β-Arrestin2 Is Critically Involved in the Differential Regulation of Phosphosignaling Pathways by Thyrotropin-Releasing Hormone and Taltirelin

. 2022 Apr 27 ; 11 (9) : . [epub] 20220427

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid35563779

In recent years, thyrotropin-releasing hormone (TRH) and its analogs, including taltirelin (TAL), have demonstrated a range of effects on the central nervous system that represent potential therapeutic agents for the treatment of various neurological disorders, including neurodegenerative diseases. However, the molecular mechanisms of their actions remain poorly understood. In this study, we investigated phosphosignaling dynamics in pituitary GH1 cells affected by TRH and TAL and the putative role of β-arrestin2 in mediating these effects. Our results revealed widespread alterations in many phosphosignaling pathways involving signal transduction via small GTPases, MAP kinases, Ser/Thr- and Tyr-protein kinases, Wnt/β-catenin, and members of the Hippo pathway. The differential TRH- or TAL-induced phosphorylation of numerous proteins suggests that these ligands exhibit some degree of biased agonism at the TRH receptor. The different phosphorylation patterns induced by TRH or TAL in β-arrestin2-deficient cells suggest that the β-arrestin2 scaffold is a key factor determining phosphorylation events after TRH receptor activation. Our results suggest that compounds that modulate kinase and phosphatase activity can be considered as additional adjuvants to enhance the potential therapeutic value of TRH or TAL.

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Tashjian A.H., Barowsky N.J., Jensen D.K. Thyrotropin releasing hormone–direct evicence for stimulation of prolactin production by pituitary cells in culture. Biochem. Biophys. Res. Commun. 1971;43:516–523. doi: 10.1016/0006-291X(71)90644-9. PubMed DOI

Kanasaki H., Oride A., Mijiddorj T., Kyo S. Role of thyrotropin-releasing hormone in prolactin-producing cell models. Neuropeptides. 2015;54:73–77. doi: 10.1016/j.npep.2015.08.001. PubMed DOI

Drastichova Z., Bourova L., Hejnova L., Jedelsky P., Svoboda P., Novotny J. Protein Alterations Induced by Long-Term Agonist Treatment of HEK293 Cells Expressing Thyrotropin-Releasing Hormone Receptor and G(11)alpha Protein. J. Cell. Biochem. 2010;109:255–264. doi: 10.1002/jcb.22409. PubMed DOI

Koo K.B., Suh H.J., Ra K.S., Choi J.W. Protective Effect of Cyclo(His-Pro) on Streptozotocin-Induced Cytotoxicity and Apoptosis In Vitro. J. Microbiol. Biotechnol. 2011;21:218–227. doi: 10.4014/jmb.1012.12003. PubMed DOI

Luo L., Luo J.Z., Jackson I. Tripeptide amide L-pyroglutamyl-histidyl-L-prolineamide (L-PHP-thyrotropin-releasing hormone, TRH) promotes insulin-producing cell proliferation. Curr. Aging Sci. 2013;6:8–13. doi: 10.2174/1874609811306010002. PubMed DOI

Faden A.I., Movsesyan V.A., Knoblach S.M., Ahmed F., Cernak B. Neuroprotective effects of novel small peptides in vitro and after brain injury. Neuropharmacology. 2005;49:410–424. doi: 10.1016/j.neuropharm.2005.04.001. PubMed DOI

Faden A.I., Knoblach S.M., Movsesyan V.A., Lea P.M., Cernak I. Novel neuroprotective tripeptides and dipeptides. Neuroprot. Agents. 2005;1053:472–481. PubMed

Jaworska-Feil L., Jantas D., Leskiewicz M., Budziszewska B., Kubera M., Basta-Kaim A., Lipkowski A.W., Lason W. Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells. Neuropeptides. 2010;44:495–508. doi: 10.1016/j.npep.2010.08.004. PubMed DOI

Daimon C.M., Chirdon P., Maudsley S., Martin B. The role of Thyrotropin Releasing Hormone in aging and neurodegenerative diseases. Am. J. Alzheimer’s Dis. 2013;1 doi: 10.7726/ajad.2013.1003. PubMed DOI PMC

Zheng C., Chen G.Q., Tan Y., Zeng W.Q., Peng Q.W., Wang J., Cheng C., Yang X.M., Nie S.K., Xu Y., et al. TRH Analog, Taltirelin Protects Dopaminergic Neurons From Neurotoxicity of MPTP and Rotenone. Front. Cell. Neurosci. 2018;12:485. doi: 10.3389/fncel.2018.00485. PubMed DOI PMC

Monga V., Meena C.L., Kaur N., Jain R. Chemistry and biology of thyrotropin-releasing hormone (TRH) and its analogs. Curr. Med. Chem. 2008;15:2718–2733. doi: 10.2174/092986708786242912. PubMed DOI

Fukuchi I., Asahi T., Kawashima K., Kawashima Y., Yamamura M., Matsuoka Y., Kinoshita K. Effects of taltirelin hydrate (TA-0910), a novel thyrotropin-releasing hormone analog, on in vivo dopamine release and turnover in rat brain. Arzneimittelforschung. 1998;48:353–359. PubMed

Thirunarayanan N., Raaka B.M., Gershengorn M.C. Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor. Front. Endocrinol. Lausanne. 2012;3:120. doi: 10.3389/fendo.2012.00120. PubMed DOI PMC

O’Dowd B.F., Lee D.K., Huang W., Nguyen T., Cheng R.G., Liu Y., Wang B., Gershengorn M.C., George S.R. TRH-R2 exhibits similar binding and acute signaling but distinct regulation and anatomic distribution compared with TRH-R1. Mol. Endocrinol. 2000;14:183–193. doi: 10.1210/mend.14.1.0407. PubMed DOI

Sun Y.H., Zupan B., Raaka B.M., Toth M., Gershengorn M.C. TRH-Receptor-Type-2-Deficient Mice are Euthyroid and Exhibit Increased Depression and Reduced Anxiety Phenotypes. Neuropsychopharmacology. 2009;34:1601–1608. doi: 10.1038/npp.2008.217. PubMed DOI PMC

Hsieh K.P., Martin T.F. Thyrotropin-releasing hormone and gonadotropin-releasing hormone receptors activate phospholipase C by coupling to the guanosine triphosphate-binding proteins Gq and G11. Mol. Endocrinol. 1992;6:1673–1681. PubMed

Hinkle P.M., Gehret A.U., Jones B.W. Desensitization, trafficking, and resensitzation of the pituitary thyrotropin-releasing hormone receptor. Front. Neurosci. 2012;6:180. doi: 10.3389/fnins.2012.00180. PubMed DOI PMC

Smith J., Yu R., Hinkle P.M. Activation of MAPK by TRH requires clathrin-dependent endocytosis and PKC but not receptor interaction with beta-arrestin or receptor endocytosis. Mol. Endocrinol. 2001;15:1539–1548. PubMed

Storey N.M., O’Bryan J.P., Armstrong D.L. Rac and Rho mediate opposing hormonal regulation of the ether-a-go-go-related potassium channel. Curr. Biol. 2002;12:27–33. doi: 10.1016/S0960-9822(01)00625-X. PubMed DOI

Romano D., Magalon K., Ciampini A., Talet C., Enjalbert A., Gerard C. Differential involvement of the Ras and Rap1 small GTPases in vasoactive intestinal and pituitary adenylyl cyclase activating polypeptides control of the prolactin gene. J. Biol. Chem. 2003;278:51386–51394. doi: 10.1074/jbc.M308372200. PubMed DOI

Jones B.W., Hinkle P.M. Beta-arrestin mediates desensitization and internalization but does not affect dephosphorylation of the thyrotropin-releasing hormone receptor. J. Biol. Chem. 2005;280:38346–38354. doi: 10.1074/jbc.M502918200. PubMed DOI

Luttrell L.M., Lefkowitz R.J. The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J. Cell Sci. 2002;115:455–465. doi: 10.1242/jcs.115.3.455. PubMed DOI

Mancini A.D., Bertrand G., Vivot K., Carpentier E., Tremblay C., Ghislain J., Bouvier M., Poitout V. beta-Arrestin Recruitment and Biased Agonism at Free Fatty Acid Receptor 1. J. Biol. Chem. 2015;290:21131–21140. doi: 10.1074/jbc.M115.644450. PubMed DOI PMC

Sanchez-Fernandez G., Cabezudo S., Garcia-Hoz C., Tobin A.B., Mayor F., Ribas C. ERK5 Activation by Gq-Coupled Muscarinic Receptors Is Independent of Receptor Internalization and beta-Arrestin Recruitment. PLoS ONE. 2013;8:e84174. doi: 10.1371/journal.pone.0084174. PubMed DOI PMC

Teixeira L.B., Parreiras-E-Silva L.T., Bruder-Nascimento T., Duarte D.A., Simoes S.C., Costa R.M., Rodriguez D.Y., Ferreira P.A.B., Silva C.A.A., Abrao E.P., et al. Ang-(1-7) is an endogenous beta-arrestin-biased agonist of the AT(1) receptor with protective action in cardiac hypertrophy. Sci. Rep. 2017;7:11903. doi: 10.1038/s41598-017-12074-3. PubMed DOI PMC

Luttrell L.M., Ferguson S.S.G., Daaka Y., Miller W.E., Maudsley S., Della Rocca G.J., Lin F.T., Kawakatsu H., Owada K., Luttrell D.K., et al. beta-arrestin-dependent formation of beta(2) adrenergic receptor Src protein kinase complexes. Science. 1999;283:655–661. doi: 10.1126/science.283.5402.655. PubMed DOI

Luttrell L.M., Roudabush F.L., Choy E.W., Miller W.E., Field M.E., Pierce K.L., Lefkowitz R.J. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc. Natl. Acad. Sci. USA. 2001;98:2449–2454. doi: 10.1073/pnas.041604898. PubMed DOI PMC

Coffa S., Breitman M., Hanson S.M., Callaway K., Kook S., Dalby K.N., Gurevich V.V. The Effect of Arrestin Conformation on the Recruitment of c-Raf1, MEK1, and ERK1/2 Activation. PLoS ONE. 2011;6:e28723. doi: 10.1371/journal.pone.0028723. PubMed DOI PMC

Cassier E., Gallay N., Bourquard T., Claeysen S., Bockaert J., Crepieux P., Poupon A., Reiter E., Marin P., Vandermoere F. Phosphorylation of beta-arrestin2 at Thr(383) by MEK underlies beta-arrestin-dependent activation of Erk1/2 by GPCRs. eLife. 2017;6:e23777. doi: 10.7554/eLife.23777. PubMed DOI PMC

Peterson Y.K., Luttrell L.M. The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling. Pharmacol. Rev. 2017;69:256–297. doi: 10.1124/pr.116.013367. PubMed DOI PMC

Ardito F., Giuliani M., Perrone D., Troiano G., Lo Muzio L. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy. Int. J. Mol. Med. 2017;40:271–280. doi: 10.3892/ijmm.2017.3036. PubMed DOI PMC

Miranda P., Giráldez T., de la Peña P., Manso D.G., Alonso-Ron C., Gómez-Varela D., Domínguez P., Barros F. Specificity of TRH receptor coupling to G-proteins for regulation of ERG K+ channels in GH3 rat anterior pituitary cells. J. Physiol. 2005;566:717–736. doi: 10.1113/jphysiol.2005.085803. PubMed DOI PMC

Qu L., Pan C., He S.M., Lang B., Gao G.D., Wang X.L., Wang Y. The Ras Superfamily of Small GTPases in Non-neoplastic Cerebral Diseases. Front. Mol. Neurosci. 2019;12:121. doi: 10.3389/fnmol.2019.00121. PubMed DOI PMC

Ba W., Nadif Kasri N. RhoGTPases at the synapse: An embarrassment of choice. Small GTPases. 2017;8:106–113. doi: 10.1080/21541248.2016.1206352. PubMed DOI PMC

Patel M., Karginov A.V. Phosphorylation-mediated regulation of GEFs for RhoA. Cell Adh. Migr. 2014;8:11–18. doi: 10.4161/cam.28058. PubMed DOI PMC

Shirakawa R., Horiuchi H. Ral GTPases: Crucial mediators of exocytosis and tumourigenesis. J. Biochem. 2015;157:285–299. doi: 10.1093/jb/mvv029. PubMed DOI

Walkup W.G., Washburn L., Sweredoski M.J., Carlisle H.J., Graham R.L., Hess S., Kennedy M.B. Phosphorylation of Synaptic GTPase-activating Protein (synGAP) by Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII) and Cyclin-dependent Kinase 5 (CDK5) Alters the Ratio of Its GAP Activity toward Ras and Rap GTPases. J. Biol. Chem. 2015;290:4908–4927. doi: 10.1074/jbc.M114.614420. PubMed DOI PMC

Humphrey S.J., Karayel O., James D.E., Mann M. High-throughput and high-sensitivity phosphoproteomics with the EasyPhos platform. Nat. Protoc. 2018;13:1897–1916. doi: 10.1038/s41596-018-0014-9. PubMed DOI

Cox J., Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 2008;26:1367–1372. doi: 10.1038/nbt.1511. PubMed DOI

Tyanova S., Temu T., Cox J. The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat. Protoc. 2016;11:2301–2319. doi: 10.1038/nprot.2016.136. PubMed DOI

Tyanova S., Temu T., Sinitcyn P., Carlson A., Hein M.Y., Geiger T., Mann M., Cox J. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Meth. 2016;13:731–740. doi: 10.1038/nmeth.3901. PubMed DOI

Kim D.H., Sarbassov D.D., Ali S.M., King J.E., Latek R.R., Erdjument-Bromage H., Tempst P., Sabatini D.M. MTOR interacts with Raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 2002;110:163–175. doi: 10.1016/S0092-8674(02)00808-5. PubMed DOI

Alers S., Loffler A.S., Wesselborg S., Stork B. Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks. Mol. Cell. Biol. 2012;32:2–11. doi: 10.1128/MCB.06159-11. PubMed DOI PMC

Pan Q., Qiao F., Gao C., Norman B., Optican L., Zelenka P.S. Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75) Cell. Mol. Life Sci. 2011;68:3425–3436. doi: 10.1007/s00018-011-0638-1. PubMed DOI PMC

Song Q., Ji Q., Li Q. The role and mechanism of beta-arrestins in cancer invasion and metastasis. Int. J. Mol. Med. 2018;41:631–639. PubMed PMC

Annunziata M.C., Parisi M., Esposito G., Fabbrocini G., Ammendola R., Cattaneo F. Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling. Int. J. Mol. Sci. 2020;21:3818. doi: 10.3390/ijms21113818. PubMed DOI PMC

Girardi C., James P., Zanin S., Pinna L.A., Ruzzene M. Differential phosphorylation of Akt1 and Akt2 by protein kinase CK2 may account for isoform specific functions. Biochim. Biophys. Acta-Mol. Cell Res. 2014;1843:1865–1874. doi: 10.1016/j.bbamcr.2014.04.020. PubMed DOI

Di Maira G., Salvi M., Arrigoni G., Marin O., Sarno S., Brustolon F., Pinna L.A., Ruzzene M. Protein kinase CK2 phosphorylates and upregulates Akt/PKB. Cell Death Differ. 2005;12:668–677. doi: 10.1038/sj.cdd.4401604. PubMed DOI

Litchfield D.W., Bosc D.G., Slominski E. The protein kinase from mitotoc human cells that phosphorylates Ser-209 on th casein kinase-II beta-subunit is P34(CDC2) Biochim. Biophys. Acta Mol. Cell Res. 1995;1269:69–78. doi: 10.1016/0167-4889(95)00100-7. PubMed DOI

Sanders S.S., De Simone F.I., Thomas G.M. mTORC1 Signaling Is Palmitoylation-Dependent in Hippocampal Neurons and Non-neuronal Cells and Involves Dynamic Palmitoylation of LAMTOR1 and mTOR. Front. Cell. Neurosci. 2019;13:115. doi: 10.3389/fncel.2019.00115. PubMed DOI PMC

Li X.D., Wang L.L., Zhou X.E., Ke J.Y., De Waal P.W., Gu X., Tan M.H.E., Wang D.Y., Wu D.H., Xu H.E., et al. Structural basis of AMPK regulation by adenine nucleotides and glycogen. Cell Res. 2015;25:50–66. doi: 10.1038/cr.2014.150. PubMed DOI PMC

Steinberg G.R., Carling D. AMP-activated protein kinase: The current landscape for drug development. Nat. Rev. Drug Discov. 2019;18:527–551. doi: 10.1038/s41573-019-0019-2. PubMed DOI

Ovens A.J., Scott J.W., Langendorf C.G., Kemp B.E., Oakhill J.S., Smiles W.J. Post-Translational Modifications of the Energy Guardian AMP-Activated Protein Kinase. Int. J. Mol. Sci. 2021;22:1229. doi: 10.3390/ijms22031229. PubMed DOI PMC

Chan E.H., Nousiainen M., Chalamalasetty R.B., Schafer A., Nigg E.A., Sillje H.H.W. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene. 2005;24:2076–2086. doi: 10.1038/sj.onc.1208445. PubMed DOI

Meng Z.P., Moroishi T., Guan K.L. Mechanisms of Hippo pathway regulation. Genes Dev. 2016;30:1–17. doi: 10.1101/gad.274027.115. PubMed DOI PMC

Yamauchi T., Moroishi T. Hippo Pathway in Mammalian Adaptive Immune System. Cells. 2019;8:398. doi: 10.3390/cells8050398. PubMed DOI PMC

Humbert N., Navaratnam N., Augert A., Da Costa M., Martien S., Wang J., Martinez D., Abbadie C., Carling D., de Launoit Y., et al. Regulation of ploidy and senescence by the AMPK-related kinase NUAK1. EMBO J. 2010;29:376–386. doi: 10.1038/emboj.2009.342. PubMed DOI PMC

Martelli A.M., Evangelisti C., Chiarini F., Grimaldi C., McCubrey J.A. The emerging role of the phosphatidylinositol 3-kinase/ akt/mammalian target of rapamycin signaling network in cancer stem cell biology. Cancers. 2010;2:1576–1596. doi: 10.3390/cancers2031576. PubMed DOI PMC

Schoneborn H., Raudzus F., Coppey M., Neumann S., Heumann R. Perspectives of RAS and RHEB GTPase Signaling Pathways in Regenerating Brain Neurons. Int. J. Mol. Sci. 2018;19:4052. doi: 10.3390/ijms19124052. PubMed DOI PMC

Young K.A., Biggins L., Sharpe H.J. Protein tyrosine phosphatases in cell adhesion. Biochem. J. 2021;478:1061–1083. doi: 10.1042/BCJ20200511. PubMed DOI PMC

Lai M.C., Chang C.M., Sun H.S. Hypoxia Induces Autophagy through Translational Up-Regulation of Lysosomal Proteins in Human Colon Cancer Cells. PLoS ONE. 2016;11:e0153627. doi: 10.1371/journal.pone.0153627. PubMed DOI PMC

Zhao H.F., Wang J., To S.S.T. The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review) Int. J. Oncol. 2015;47:429–436. doi: 10.3892/ijo.2015.3052. PubMed DOI

Alsaqati M., Heine V.M., Harwood A.J. Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation. Mol. Autism. 2020;11:80. doi: 10.1186/s13229-020-00391-w. PubMed DOI PMC

Goel S., DeCristo M.J., McAllister S.S., Zhao J.J. CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest. Trends Cell Biol. 2018;28:911–925. doi: 10.1016/j.tcb.2018.07.002. PubMed DOI PMC

Won S.Y., Park J.J., Shin E.Y., Kim E.G. PAK4 signaling in health and disease: Defining the PAK4-CREB axis. Exp. Mol. Med. 2019;51:1–9. doi: 10.1038/s12276-018-0204-0. PubMed DOI PMC

Kucerova L., Kubrak O.I., Bengtsson J.M., Strnad H., Nylin S., Theopold U., Nassel D.R. Slowed aging during reproductive dormancy is reflected in genome-wide transcriptome changes in Drosophila melanogaster. BMC Genom. 2016;17:50. doi: 10.1186/s12864-016-2383-1. PubMed DOI PMC

Sanchez A.M.J., Candau R.B., Csibi A., Pagano A.F., Raibon A., Bernardi H. The role of AMP-activated protein kinase in the coordination of skeletal muscle turnover and energy homeostasis. Am. J. Physiol.-Cell Physiol. 2012;303:C475–C485. doi: 10.1152/ajpcell.00125.2012. PubMed DOI

Mihaylova M.M., Shaw R.J. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol. 2011;13:1016–1023. doi: 10.1038/ncb2329. PubMed DOI PMC

Fang C.Y., Lai T.C., Hsiao M., Chang Y.C. The Diverse Roles of TAO Kinases in Health and Diseases. Int. J. Mol. Sci. 2020;21:7463. doi: 10.3390/ijms21207463. PubMed DOI PMC

Spencer J.P.E. The interactions of flavonoids within neuronal signalling pathways. Genes Nutr. 2007;2:257–273. doi: 10.1007/s12263-007-0056-z. PubMed DOI PMC

Cuesta C., Arevalo-Alameda C., Castellano E. The Importance of Being PI3K in the RAS Signaling Network. Genes. 2021;12:1094. doi: 10.3390/genes12071094. PubMed DOI PMC

Beck T.N., Nicolas E., Kopp M.C., Golemis E.A. Adaptors for disorders of the brain? The cancer signaling proteins NEDD9, CASS4, and PTK2B in Alzheimer’s disease. Oncoscience. 2014;1:486–503. doi: 10.18632/oncoscience.64. PubMed DOI PMC

Lock L.S., Frigault M.M., Saucier C., Park M. Grb2-independent recruitment of Gab1 requires the C-terminal lobe and structural integrity of the met receptor kinase domain. J. Biol. Chem. 2003;278:30083–30090. doi: 10.1074/jbc.M302675200. PubMed DOI

Nakamura Y., Hibino K., Yanagida T., Sako Y. Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains. Biophys. Physicobiol. 2016;13:1–11. doi: 10.2142/biophysico.13.0_1. PubMed DOI PMC

Lepri F., De Luca A., Stella L., Rossi C., Baldassarre G., Pantaleoni F., Cordeddu V., Williams B.J., Dentici M.L., Caputo V., et al. SOS1 Mutations in Noonan Syndrome: Molecular Spectrum, Structural Insights on Pathogenic Effects, and Genotype-Phenotype Correlations. Hum. Mutat. 2011;32:760–772. doi: 10.1002/humu.21492. PubMed DOI PMC

Lavoie H., Sahmi M., Maisonneuve P., Marullo S.A., Thevakumaran N., Jin T., Kurinov I., Sicheri F., Therrien M. MEK drives BRAF activation through allosteric control of KSR proteins. Nature. 2018;554:549–553. doi: 10.1038/nature25478. PubMed DOI PMC

Dougherty M.K., Ritt D.A., Zhou M., Specht S.I., Monson D.M., Veenstra T.D., Morrison D.K. KSR2 Is a Calcineurin Substrate that Promotes ERK Cascade Activation in Response to Calcium Signals. Mol. Cell. 2009;34:652–662. doi: 10.1016/j.molcel.2009.06.001. PubMed DOI PMC

Nishiyama K., Maekawa M., Nakagita T., Nakayama J., Kiyoi T., Chosei M., Murakami A., Kamei Y., Takeda H., Takada Y., et al. CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP. Life Sci. Alliance. 2021;4:e202101095. doi: 10.26508/lsa.202101095. PubMed DOI PMC

Cerezo E.L., Houles T., Lie O., Sarthou M.K., Audoynaud C., Lavoie G., Halladjian M., Cantaloube S., Froment C., Burlet-Schiltz O., et al. RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit. PLoS Genet. 2021;17:e1009583. doi: 10.1371/journal.pgen.1009583. PubMed DOI PMC

Deng Y.N., Xia Z.J., Zhang P., Ejaz S., Liang S.F. Transcription Factor RREB1: From Target Genes towards Biological Functions. Int. J. Biol. Sci. 2020;16:1463–1473. doi: 10.7150/ijbs.40834. PubMed DOI PMC

Agulto R.L., Rogers M.M., Tan T.C., Ramkumar A., Downing A.M., Bodin H., Castro J., Nowakowski D.W., Ori-McKenney K.M. Autoregulatory control of microtubule binding in doublecortin-like kinase 1. eLife. 2021;10:e60126. doi: 10.7554/eLife.60126. PubMed DOI PMC

Weygant N., Qu D.F., Berry W.L., May R., Chandrakesan P., Owen D.B., Sureban S.M., Ali N., Janknecht R., Houchen C.W. Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1. Mol. Cancer. 2014;13:103. doi: 10.1186/1476-4598-13-103. PubMed DOI PMC

Patel O., Dai W.W., Mentzel M., Griffin M.D.W., Serindoux J., Gay Y., Fischer S., Sterle S., Kropp A., Burns C.J., et al. Biochemical and Structural Insights into Doublecortin-like Kinase Domain 1. Structure. 2016;24:1550–1561. doi: 10.1016/j.str.2016.07.008. PubMed DOI

Sureban S.M., May R., Qu D.F., Weygant N., Chandrakesan P., Ali N., Lightfoot S.A., Pantazis P., Rao C.V., Postier R.G., et al. DCLK1 Regulates Pluripotency and Angiogenic Factors via microRNA-Dependent Mechanisms in Pancreatic Cancer. PLoS ONE. 2013;8:e73940. doi: 10.1371/journal.pone.0073940. PubMed DOI PMC

Kent O.A., Fox-Talbot K., Halusha M.K. RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targets. Oncogene. 2013;32:2576–2585. doi: 10.1038/onc.2012.266. PubMed DOI PMC

Namba T., Funahashi Y., Nakamuta S., Xu C., Takano T., Kaibuchi K. Exztacellular and intracellular signaling for neuronal polarity. Physiol. Rev. 2015;95:995–1024. doi: 10.1152/physrev.00025.2014. PubMed DOI

Llavero F., Arrazola Sastre A., Luque Montoro M., Martín M.A., Arenas J., Lucia A., Zugaza J.L. Small GTPases of the Ras superfamily and glycogen phosphorylase regulation in T cells. Small GTPases. 2021;12:106–113. doi: 10.1080/21541248.2019.1665968. PubMed DOI PMC

Llavero F., Montoro M.L., Sastre A.A., Fernandez-Moreno D., Lacerda H.M., Parada L.A., Lucia A., Zugaza J.L. Epidermal growth factor receptor controls glycogen phosphorylase in T cells through small GTPases of the RAS family. J. Biol. Chem. 2019;294:4345–4358. doi: 10.1074/jbc.RA118.005997. PubMed DOI PMC

Bok S., Shin D.Y., Yallowitz A.R., Eiseman M., Cung M., Xu R., Li N., Sun J., Williams A.L., Scott J.E., et al. MEKK2 mediates aberrant ERK activation in neurofibromatosis type I. Nat. Commun. 2020;11:5704. doi: 10.1038/s41467-020-19555-6. PubMed DOI PMC

Kishida S., Yamamoto H., Hino S., Ikeda S., Kishida M., Kikuchi A. DIX domains of Dvl and Axin are necessary for protein interactions and their ability to regulate beta-catenin stability. Mol. Cell. Biol. 1999;19:4414–4422. doi: 10.1128/MCB.19.6.4414. PubMed DOI PMC

Bros M., Haas K., Moll L., Grabbe S. RhoA as a Key Regulator of Innate and Adaptive Immunity. Cells. 2019;8:733. doi: 10.3390/cells8070733. PubMed DOI PMC

Li Y.Y., Shi J.H., Yang J., Ge S.F., Zhang J.M., Jia R.B., Fan X.Q. Uveal melanoma: Progress in molecular biology and therapeutics. Ther. Adv. Med. Oncol. 2020;12:1758835920965852. doi: 10.1177/1758835920965852. PubMed DOI PMC

Yi F.S., Kong R.R., Ren J.Q., Zhu L., Lou J.Z., Wu J.Y., Feng W. Noncanonical Myo9b-RhoGAP Accelerates RhoA GTP Hydrolysis by a Dual-Arginine-Finger Mechanism. J. Mol. Biol. 2016;428:3043–3057. doi: 10.1016/j.jmb.2016.06.014. PubMed DOI PMC

Schlessinger K., Hall A., Tolwinski N. Wnt signaling pathways meet Rho GTPases. Genes Dev. 2009;23:265–277. doi: 10.1101/gad.1760809. PubMed DOI

Cook D.R., Rossman K.L., Der C.J. Rho guanine nucleotide exchange factors: Regulators of Rho GTPase activity in development and disease. Oncogene. 2014;33:4021–4035. doi: 10.1038/onc.2013.362. PubMed DOI PMC

Blangy A. Tensins are versatile regulators of Rho GTPase signalling and cell adhesion. Biol. Cell. 2017;109:115–126. doi: 10.1111/boc.201600053. PubMed DOI

Gong X.W., Didan Y., Lock J.G., Stromblad S. KIF13A-regulated RhoB plasma membrane localization governs membrane blebbing and blebby amoeboid cell migration. EMBO J. 2018;37:e98994. doi: 10.15252/embj.201898994. PubMed DOI PMC

Maiwald S., Motazacker M.M., van Capelleveen J.C., Sivapalaratnam S., van der Wal A.C., van der Loos C., Kastelein J.J.P., Ouwehand W.H., Hovingh G.K., Trip M.D., et al. A rare variant in MCF2L identified using exclusion linkage in a pedigree with premature atherosclerosis. Eur. J. Hum. Genet. 2016;24:86–91. doi: 10.1038/ejhg.2015.70. PubMed DOI PMC

Akizu N., Martínez-Balbás M.A. EZH2 orchestrates apicobasal polarity and neuroepithelial cell renewal. Neurogenesis. 2016;3:e1250034. doi: 10.1080/23262133.2016.1250034. PubMed DOI PMC

Feng X.D., Degese M.S., Iglesias-Bartolome R., Vaque J.P., Molinolo A.A., Rodrigues M., Zaidi M.R., Ksander B.R., Merlino G., Sodhi A., et al. Hippo-Independent Activation of YAP by the GNAQ Uveal Melanoma Oncogene through a Trio-Regulated Rho GTPase Signaling Circuitry. Cancer Cell. 2014;25:831–845. doi: 10.1016/j.ccr.2014.04.016. PubMed DOI PMC

Muller P.M., Rademacher J., Bagshaw R.D., Wortmann C., Barth C., van Unen J., Alp K.M., Giudice G., Eccles R.L., Heinrich L.E., et al. Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nat. Cell Biol. 2020;22:498–511. doi: 10.1038/s41556-020-0488-x. PubMed DOI

Kim S.I., Kim H.J., Han D.C., Lee H.B. Effect of lovastatin on small GTP binding proteins and on TGF-beta 1 and fibronectin expression. Kidney Int. 2000;58:S88–S92. doi: 10.1046/j.1523-1755.2000.07714.x. PubMed DOI

Shimizu A., Mammoto A., Italiano J.E., Pravda E., Dudley A.C., Ingber D.E., Klagsbrun M. ABL2/ARG tyrosine kinase mediates SEMA3F-induced RhoA inactivation and cytoskeleton collapse in human glioma cells. J. Biol. Chem. 2008;283:27230–27238. doi: 10.1074/jbc.M804520200. PubMed DOI PMC

Lartey J., Bernal A.L. RHO protein regulation of contraction in the human uterus. Reproduction. 2009;138:407–424. doi: 10.1530/REP-09-0160. PubMed DOI

Cossette S.M., Bhute V.J., Bao X., Harmann L.M., Horswill M.A., Sinha I., Gastonguay A., Pooya S., Bordas M., Kumar S.N., et al. Sucrose Nonfermenting-Related Kinase Enzyme-Mediated Rho-Associated Kinase Signaling is Responsible for Cardiac Function. Circ.-Cardiovasc. Genet. 2016;9:474–486. doi: 10.1161/CIRCGENETICS.116.001515. PubMed DOI PMC

Fokin A.I., Klementeva T.S., Nadezhdina E.S., Burakov A.V. SLK/LOSK kinase regulates cell motility independently of microtubule organization and Golgi polarization. Cytoskeleton. 2016;73:83–92. doi: 10.1002/cm.21276. PubMed DOI

Rangamani P., Levy M.G., Khan S., Oster G. Paradoxical signaling regulates structural plasticity in dendritic spines. Proc. Natl. Acad. Sci. USA. 2016;113:E5298–E5307. doi: 10.1073/pnas.1610391113. PubMed DOI PMC

Durkin C.H., Leite F., Cordeiro J.V., Handa Y., Arakawa Y., Valderrama F., Way M. RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6. Dev. Cell. 2017;41:315–329. doi: 10.1016/j.devcel.2017.04.010. PubMed DOI PMC

Eisler S.A., Curado F., Link G., Schulz S., Noack M., Steinke M., Olayioye M.A., Hausser A. A Rho signaling network links microtubules to PKD controlled carrier transport to focal adhesions. eLife. 2018;7:e35907. doi: 10.7554/eLife.35907. PubMed DOI PMC

Forrest M.P., Parnell E., Penzes P. Dendritic structural plasticity and neuropsychiatric disease. Nat. Rev. Neurosci. 2018;19:215–234. doi: 10.1038/nrn.2018.16. PubMed DOI PMC

Kurtzeborn K., Kwon H.N., Kuure S. MAPK/ERK Signaling in Regulation of Renal Differentiation. Int. J. Mol. Sci. 2019;20:1779. doi: 10.3390/ijms20071779. PubMed DOI PMC

Pedraza N., Cemeli T., Monserrat M.V., Garí E., Ferrezuelo F. Regulation of small GTPase activity by G1 cyclins. Small GTPases. 2019;10:47–53. doi: 10.1080/21541248.2016.1268665. PubMed DOI PMC

Asih P.R., Prikas E., Stefanoska K., Tan A.R.P., Ahel H.I., Ittner A. Functions of p38 MAP Kinases in the Central Nervous System. Front. Mol. Neurosci. 2020;13:570586. doi: 10.3389/fnmol.2020.570586. PubMed DOI PMC

Schulte G., Shenoy S.K. beta-Arrestin and dishevelled coordinate biased signaling. Proc. Natl. Acad. Sci. USA. 2011;108:19839–19840. doi: 10.1073/pnas.1117444108. PubMed DOI PMC

Clayton N.S., Ridley A.J. Targeting Rho GTPase Signaling Networks in Cancer. Front. Cell Dev. Biol. 2020;8:222. doi: 10.3389/fcell.2020.00222. PubMed DOI PMC

Tolias K.F., Duman J.G., Um K. Control of synapse development and plasticity by Rho GTPase regulatory proteins. Prog. Neurobiol. 2011;94:133–148. doi: 10.1016/j.pneurobio.2011.04.011. PubMed DOI PMC

Kovacs J.J., Hara M.R., Davenport C.L., Kim J., Lefkowitz R.J. Arrestin Development: Emerging Roles for beta-arrestins in Developmental Signaling Pathways. Dev. Cell. 2009;17:443–458. doi: 10.1016/j.devcel.2009.09.011. PubMed DOI PMC

Bryja V., Schambony A., Cajanek L., Dominguez I., Arenas E., Schulte G. beta-Arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways. EMBO Rep. 2008;9:1244–1250. doi: 10.1038/embor.2008.193. PubMed DOI PMC

Moniz S., Jordan P. Emerging roles for WNK kinases in cancer. Cell. Mol. Life Sci. 2010;67:1265–1276. doi: 10.1007/s00018-010-0261-6. PubMed DOI PMC

Arias-Romero L.E., Villamar-Cruz O., Pacheco A., Kosoff R., Huang M., Muthuswamy S.K., Chernoff J. A Rac-Pak signaling pathway is essential for ErbB2-mediated transformation of human breast epithelial cancer cells. Oncogene. 2010;29:5839–5849. doi: 10.1038/onc.2010.318. PubMed DOI PMC

Tobon A.L., Suresh M., Jin J., Vitriolo A., Pietralla T., Tedford K., Bossenz M., Mahnken K., Kiefer F., Testa G., et al. The guanine nucleotide exchange factor Arhgef7/beta Pix promotes axon formation upstream of TC10. Sci. Rep. 2018;8:8811. doi: 10.1038/s41598-018-27081-1. PubMed DOI PMC

Arash E.H., Song K.M., Song S., Shiban A., Attisano L. Arhgef7 promotes activation of the Hippo pathway core kinase Lats. EMBO J. 2014;33:2997–3011. doi: 10.15252/embj.201490230. PubMed DOI PMC

Fu X.D. Both sides of the same coin: Rac1 splicing regulating by EGF signaling. Cell Res. 2017;27:455–456. doi: 10.1038/cr.2017.19. PubMed DOI PMC

Miyamoto Y., Yamauchi J., Sanbe A., Tanoue A. Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth. Exp. Cell Res. 2007;313:791–804. doi: 10.1016/j.yexcr.2006.11.017. PubMed DOI

Lee S.Y., Kim H., Kim K., Lee H., Lee S., Lee D. Arhgap17, a RhoGTPase activating protein, regulates mucosal and epithelial barrier function in the mouse colon. Sci. Rep. 2016;6:26923. doi: 10.1038/srep26923. PubMed DOI PMC

Okabe T., Nakamura T., Nishimura Y.N., Kohu K., Ohwada S., Morishita Y., Akiyama T. RICS, a novel GTPase-activating protein for Cdc42 and Rac1, is involved in the beta-catenin-N-cadherin and N-methyl-D-aspartate receptor signaling. J. Biol. Chem. 2003;278:9920–9927. doi: 10.1074/jbc.M208872200. PubMed DOI

Harden T.K., Hicks S.N., Sondek J. Phospholipase C isozymes as effectors of Ras superfamily GTPases. J. Lipid Res. 2009;50:S243–S248. doi: 10.1194/jlr.R800045-JLR200. PubMed DOI PMC

Kichina J.V., Goc A., Al-Husein B., Somanath P.R., Kandel E.S. PAK1 as a therapeutic target. Expert Opin. Ther. Targets. 2010;14:703–725. doi: 10.1517/14728222.2010.492779. PubMed DOI PMC

He X.J., Kuo Y.C., Rosche T.J., Zhang X.W. Structural Basis for Autoinhibition of the Guanine Nucleotide Exchange Factor FARP2. Structure. 2013;21:355–364. doi: 10.1016/j.str.2013.01.001. PubMed DOI PMC

Kuijl C., Pilli M., Alahari S.K., Janssen H., Khoo P.S., Ervin K.E., Calero M., Jonnalagadda S., Scheller R.H., Neefjes J., et al. Rac and Rab GTPases dual effector Nischarin regulates vesicle maturation to facilitate survival of intracellular bacteria. EMBO J. 2013;32:713–727. doi: 10.1038/emboj.2013.10. PubMed DOI PMC

Lopez-Guerrero A.M., Espinosa-Bermejo N., Sanchez-Lopez I., Macartney T., Pascual-Caro C., Orantos-Aguilera Y., Rodriguez-Ruiz L., Perez-Oliva A.B., Mulero V., Pozo-Guisado E., et al. RAC1-Dependent ORAI1 Translocation to the Leading Edge Supports Lamellipodia Formation and Directional Persistence. Sci. Rep. 2020;10:6580. doi: 10.1038/s41598-020-63353-5. PubMed DOI PMC

Vasco V.R.L.L. Phosphoinositide Signal Transduction Pathway and Osteosarcoma Metastases. Jentashapir J. Cell. Mol. Biol. 2021;12:e116225. doi: 10.5812/jjcmb.116225. DOI

Zamboni V., Jones R., Umbach A., Ammoni A., Passafaro M., Hirsch E., Merlo G.R. Rho GTPases in Intellectual Disability: From Genetics to Therapeutic Opportunities. Int. J. Mol. Sci. 2018;19:1821. doi: 10.3390/ijms19061821. PubMed DOI PMC

Wang S.E., Xian B., Guix M., Olivares M.G., Parker J., Chung C.H., Pandiella A., Arteaga C.L. Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Mol. Cell. Biol. 2008;28:5605–5620. doi: 10.1128/MCB.00787-08. PubMed DOI PMC

Manchanda P.K., Jones G.N., Lee A.A., Pringle D.R., Zhang M., Yu L., La Perle K.M.D., Kirschner L.S. Rac1 is required for Prkar1a-mediated Nf2 suppression in Schwann cell tumors. Oncogene. 2013;32:3491–3499. doi: 10.1038/onc.2012.374. PubMed DOI PMC

Lopez-Haber C., Barrio-Real L., Casado-Medrano V., Kazanietz M.G. Heregulin/ErbB3 Signaling Enhances CXCR4-Driven Rac1 Activation and Breast Cancer Cell Motility via Hypoxia-Inducible Factor 1 alpha. Mol. Cell. Biol. 2016;36:2011–2026. doi: 10.1128/MCB.00180-16. PubMed DOI PMC

Nuche-Berenguer B., Ramos-Alvarez I., Jensen R.T. The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events. Biochim. Biophys. Acta-Mol. Basis Dis. 2016;1862:1122–1136. doi: 10.1016/j.bbadis.2016.02.008. PubMed DOI PMC

Mertens A.E., Roovers R.C., Collard J.G. Regulation of Tiam1-Rac signalling. FEBS Lett. 2003;546:11–16. doi: 10.1016/S0014-5793(03)00435-6. PubMed DOI

Heo J., Thapar R., Campbell S.L. Recognition and activation of rho GTPases by Vav1 and Vav2 guanine nucleotide exchange factors. Biochemistry. 2005;44:6573–6585. doi: 10.1021/bi047443q. PubMed DOI

Kukimoto-Niino M., Tsuda K., Ihara K., Mishima-Tsumagari C., Honda K., Ohsawa N., Shirouzu M. Structural Basis for the Dual Substrate Specificity of DOCK7 Guanine Nucleotide Exchange Factor. Structure. 2019;27:741–748. doi: 10.1016/j.str.2019.02.001. PubMed DOI

Chen Q.A., Zhu Y.C., Yu J., Miao S., Zheng J., Xu L., Zhou Y., Li D., Zhang C., Tao J., et al. CDKL5, a Protein Associated with Rett Syndrome, Regulates Neuronal Morphogenesis via Rac1 Signaling. J. Neurosci. 2010;30:12777–12786. doi: 10.1523/JNEUROSCI.1102-10.2010. PubMed DOI PMC

Welch H.C. Regulation and function of P-Rex family Rac-GEFs. Small GTPases. 2015;6:49–70. doi: 10.4161/21541248.2014.973770. PubMed DOI PMC

Offenhauser N., Borgonovo A., Disanza A., Romano P., Ponzanelli I., Iannolo G., Di Fiore P.P., Scita G. The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway. Mol. Biol. Cell. 2004;15:91–98. doi: 10.1091/mbc.e03-06-0427. PubMed DOI PMC

Yu D., Makkar G., Strickland D.K., Blanpied T.A., Stumpo D.J., Blackshear P.J., Sarkar R., Monahan T.S. Myristoylated Alanine-Rich Protein Kinase Substrate (MARCKS) Regulates Small GTPase Rac1 and Cdc42 Activity and Is a Critical Mediator of Vascular Smooth Muscle Cell Migration in Intimal Hyperplasia Formation. J. Am. Heart Assoc. 2015;4:e002255. doi: 10.1161/JAHA.115.002255. PubMed DOI PMC

Nola S., Sebbagh M., Marchetto S., Osmani N., Nourry C., Audebert S., Navarro C., Rachel R., Montcouquiol M., Sans N., et al. Scrib regulates PAK activity during the cell migration process. Hum. Mol. Genet. 2008;17:3552–3565. doi: 10.1093/hmg/ddn248. PubMed DOI

Shirafuji T., Ueyama T., Yoshino K., Takahashi H., Adachi N., Ago Y., Koda K., Nashida T., Hiramatsu N., Matsuda T., et al. The Role of Pak-Interacting Exchange Factor-beta Phosphorylation at Serines 340 and 583 by PKC gamma in Dopamine Release. J. Neurosci. 2014;34:9268–9280. doi: 10.1523/JNEUROSCI.4278-13.2014. PubMed DOI PMC

Zhou W., Li X.B., Premont R.T. Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT-PIX complexes. J. Cell Sci. 2016;129:1963–1974. doi: 10.1242/jcs.179465. PubMed DOI PMC

Webb D.J., Mayhew M.W., Kovalenko M., Schroeder M.J., Jeffery E.D., Whitmore L., Shabanowitz J., Hunt D.F., Horwitz A.F. Identification of phosphorylation sites in GIT1. J. Cell Sci. 2006;119:2847–2850. doi: 10.1242/jcs.03044. PubMed DOI

Tran C.W., Saibil S.D., Le Bihan T., Hamilton S.R., Lang K.S., You H., Lin A.E., Garza K.M., Elford A.R., Tai K., et al. Glycogen Synthase Kinase-3 Modulates Cbl-b and Constrains T Cell Activation. J. Immunol. 2017;199:4056–4065. doi: 10.4049/jimmunol.1600396. PubMed DOI

Richnau N., Aspenstrom P. RICH, a rho GTPase-activating protein domain-containing protein involved in signaling by Cdc42 and Rac1. J. Biol. Chem. 2001;276:35060–35070. doi: 10.1074/jbc.M103540200. PubMed DOI

Fortin S.P., Ennis M.J., Schumacher C.A., Zylstra-Diegel C.R., Williams B.O., Ross J.T.D., Winkles J.A., Loftus J.C., Symons M.H., Tran N.L. Cdc42 and the Guanine Nucleotide Exchange Factors Ect2 and Trio Mediate Fn14-Induced Migration and Invasion of Glioblastoma Cells. Mol. Cancer Res. 2012;10:958–968. doi: 10.1158/1541-7786.MCR-11-0616. PubMed DOI PMC

Masaki T. Polarization and myelination in myelinating glia. ISRN Neurol. 2012;2012:769412. doi: 10.5402/2012/769412. PubMed DOI PMC

Chen Y., Liang Z.Y., Fei E.K., Chen Y.W., Zhou X.P., Fang W.Q., Fu W.Y., Fu A.K.Y., Ip N.Y. Axin Regulates Dendritic Spine Morphogenesis through Cdc42-Dependent Signaling. PLoS ONE. 2015;10:e0133115. doi: 10.1371/journal.pone.0133115. PubMed DOI PMC

Brudvig J.J., Cain J.T., Sears R.M., Schmidt-Grimminger G.G., Wittchen E.S., Adler K.B., Ghashghaei H.T., Weimer J.M. MARCKS regulates neuritogenesis and interacts with a CDC42 signaling network. Sci. Rep. 2018;8:13278. doi: 10.1038/s41598-018-31578-0. PubMed DOI PMC

Farrugia A.J., Calvo F. The Borg family of Cdc42 effector proteins Cdc42EP1-5. Biochem. Soc. Trans. 2016;44:1709–1716. doi: 10.1042/BST20160219. PubMed DOI PMC

Boissier P., Huynh-Do U. The guanine nucleotide exchange factor Tiam1: A Janus-faced molecule in cellular signaling. Cell Signal. 2014;26:483–491. doi: 10.1016/j.cellsig.2013.11.034. PubMed DOI

Lai F.P.L., Szczodrak M., Oelkers J.M., Ladwein M., Acconcia F., Benesch S., Auinger S., Faix J., Small J.V., Polo S., et al. Cortactin Promotes Migration and Platelet-derived Growth Factor-induced Actin Reorganization by Signaling to Rho-GTPases. Mol. Biol. Cell. 2009;20:3209–3223. doi: 10.1091/mbc.e08-12-1180. PubMed DOI PMC

Eiseler T., Wille C., Koehler C., Illing A., Seufferlein T. Protein Kinase D2 Assembles a Multiprotein Complex at the Trans-Golgi Network to Regulate Matrix Metalloproteinase Secretion. J. Biol. Chem. 2016;291:462–477. doi: 10.1074/jbc.M115.673582. PubMed DOI PMC

Boulay P.L., Cotton M., Melancon P., Claing A. ADP-ribosylation Factor 1 Controls the Activation of the Phosphatidylinositol 3-Kinase Pathway to Regulate Epidermal Growth Factor-dependent Growth and Migration of Breast Cancer Cells. J. Biol. Chem. 2008;283:36425–36434. doi: 10.1074/jbc.M803603200. PubMed DOI PMC

Schoppe J., Schubert E., Apelbaum A., Yavavli E., Birkholz O., Stephanowitz H., Han Y.P., Perz A., Hofnagel O., Liu F., et al. Flexible open conformation of the AP-3 complex explains its role in cargo recruitment at the Golgi. J. Biol. Chem. 2021;297:101334. doi: 10.1016/j.jbc.2021.101334. PubMed DOI PMC

Piccini A., Castroflorio E., Valente P., Guarnieri F.C., Aprile D., Michetti C., Bramini M., Giansante G., Pinto B., Savardi A., et al. APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development. Cell Rep. 2017;21:3596–3611. doi: 10.1016/j.celrep.2017.11.073. PubMed DOI

Schürmann B., Bermingham D.P., Kopeikina K.J., Myczek K., Yoon S., Horan K.E., Kelly C.J., Martin-de-Saavedra M.D., Forrest M.P., Fawcett-Patel J.M., et al. A novel role for the late-onset Alzheimer’s disease (LOAD)-associated protein Bin1 in regulating postsynaptic trafficking and glutamatergic signaling. Mol. Psychiatry. 2020;25:2000–2016. doi: 10.1038/s41380-019-0407-3. PubMed DOI PMC

Monetta P., Slavin F., Romero N., Alvarez C. Rab1b interacts with GBF1 and modulates both ARR dynamics and COPI association. Mol. Biol. Cell. 2007;18:2400–2410. doi: 10.1091/mbc.e06-11-1005. PubMed DOI PMC

Sztul E., Chen P.W., Casanova J.E., Cherfils J., Decks J.B., Lambright D.G., Lee F.J.S., Randazzo P.A., Santy L.C., Schurmann A., et al. ARF GTPases and their GEFs and GAPs: Concepts and challenges. Mol. Biol. Cell. 2019;30:1249–1271. doi: 10.1091/mbc.E18-12-0820. PubMed DOI PMC

Villarroel-Campos D., Bronfman F.C., Gonzalez-Billault C. Rab GTPase Signaling in Neurite Outgrowth and Axon Specification. Cytoskeleton. 2016;73:498–507. doi: 10.1002/cm.21303. PubMed DOI

Xiaofeng D., Shuanglin X. Endocytosis and human innate immunity. J. Immunol. Sci. 2018;2:65–70.

Lohr N.L. Collateral development: The quest continues. Circ. Res. 2014;114:591–593. doi: 10.1161/CIRCRESAHA.114.303402. PubMed DOI

Cezanne A., Lauer J., Solomatina A., Sbalzarini I.F., Zerial M. A non-linear system patterns Rab5 GTPase on the membrane. eLife. 2020;9:e54434. doi: 10.7554/eLife.54434. PubMed DOI PMC

Li Z., Zhao K., Lv X.L., Lan Y.G., Hu S.Y., Shi J.C., Guan J.Y., Yang Y.W., Lu H.J., He H.B., et al. Ulk1 Governs Nerve Growth Factor/TrkA Signaling by Mediating Rab5 GTPase Activation in Porcine Hemagglutinating Encephalomyelitis Virus-Induced Neurodegenerative Disorders. J. Virol. 2018;92:e00325-18. doi: 10.1128/JVI.00325-18. PubMed DOI PMC

Lyon A.M., Dutta S., Boguth C.A., Skiniotis G., Tesmer J.J.G. Full-length G alpha(q)-phospholipase C-beta 3 structure reveals interfaces of the C-terminal coiled-coil domain. Nat. Struct. Mol. Biol. 2013;20:355–362. doi: 10.1038/nsmb.2497. PubMed DOI PMC

van den Eshof B.L., Hoogendijk A.J., Simpson P.J., van Alphen F.P.J., Zanivan S., Mertens K., Meijer A.B., van den Biggelaar M. Paradigm of Biased PAR1 (Protease-Activated Receptor-1) Activation and Inhibition in Endothelial Cells Dissected by Phosphoproteomics. Arterioscler. Thromb. Vasc. Biol. 2017;37:1891–1902. doi: 10.1161/ATVBAHA.117.309926. PubMed DOI

Nielsen E., Christoforidis S., Uttenweiler-Joseph S., Miaczynska M., Dewitte F., Wilm M., Hoflack B., Zerial M. Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain. J. Cell Biol. 2000;151:601–612. doi: 10.1083/jcb.151.3.601. PubMed DOI PMC

Eathiraj S., Pan X.J., Ritacco C., Lambright D.G. Structural basis of family-wide Rab GTPase recognition by rabenosyn-5. Nature. 2005;436:415–419. doi: 10.1038/nature03798. PubMed DOI PMC

Grant B.D., Donaldson J.G. Pathways and mechanisms of endocytic recycling. Nat. Rev. Mol. Cell Biol. 2009;10:597–608. doi: 10.1038/nrm2755. PubMed DOI PMC

Linford A., Yoshimura S., Bastos R.N., Langemeyer L., Gerondopoulos A., Rigden D.J., Barr F.A. Rab14 and Its Exchange Factor FAM116 Link Endocytic Recycling and Adherens Junction Stability in Migrating Cells. Dev. Cell. 2012;22:952–966. doi: 10.1016/j.devcel.2012.04.010. PubMed DOI PMC

Chaineau M., Ioannou M.S., McPherson P.S. Rab35: GEFs, GAPs and Effectors. Traffic. 2013;14:1109–1117. doi: 10.1111/tra.12096. PubMed DOI

Fuchs E., Haas A.K., Spooner R.A., Yoshimura S.I., Lord J.M., Barr F.A. Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways. J. Cell Biol. 2007;177:1133–1143. doi: 10.1083/jcb.200612068. PubMed DOI PMC

Gallo L.I., Liao Y., Ruiz W.G., Clayton D.R., Li M., Liu Y.J., Jiang Y., Fukuda M., Apodaca G., Yin X.M. TBC1D9B functions as a GTPase-activating protein for Rab11a in polarized MDCK cells. Mol. Biol. Cell. 2014;25:3779–3797. doi: 10.1091/mbc.e13-10-0604. PubMed DOI PMC

Spearman P. Viral interactions with host cell Rab GTPases. Small GTPases. 2018;9:192–201. doi: 10.1080/21541248.2017.1346552. PubMed DOI PMC

Tzeng H.T., Wang Y.C. Rab-mediated vesicle trafficking in cancer. J. Biomed. Sci. 2016;23:70. doi: 10.1186/s12929-016-0287-7. PubMed DOI PMC

Elbaz-Alon Y., Guo Y.T., Segev N., Harel M., Quinnell D.E., Geiger T., Avinoam O., Li D., Nunnari J. PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria. Nat. Commun. 2020;11:3645. doi: 10.1038/s41467-020-17451-7. PubMed DOI PMC

Matsui T., Fukuda M. Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4. EMBO Rep. 2013;14:450–457. doi: 10.1038/embor.2013.32. PubMed DOI PMC

Nassari S., Del Olmo T., Jean S. Rabs in Signaling and Embryonic Development. Int. J. Mol. Sci. 2020;21:1064. doi: 10.3390/ijms21031064. PubMed DOI PMC

Zachari M., Ganley I.G. The mammalian ULK1 complex and autophagy initiation. Signal. Mech. Autophagy. 2017;61:585–596. PubMed PMC

Wang C.Y., Wang H.F., Zhang D.Y., Luo W.W., Liu R.L., Xu D.Q., Diao L., Liao L.J., Liu Z.X. Phosphorylation of ULK1 affects autophagosome fusion and links chaperone-mediated autophagy to macroautophagy. Nat. Commun. 2018;9:3492. doi: 10.1038/s41467-018-05449-1. PubMed DOI PMC

Marat A.L., Dokainish H., McPherson P.S. DENN Domain Proteins: Regulators of Rab GTPases. J. Biol. Chem. 2011;286:13791–13800. doi: 10.1074/jbc.R110.217067. PubMed DOI PMC

Kiral F.R., Kohrs F.E., Jin E.J., Hiesinger P.R. Rab GTPases and Membrane Trafficking in Neurodegeneration. Curr. Biol. 2018;28:R471–R486. doi: 10.1016/j.cub.2018.02.010. PubMed DOI PMC

Ghelfi E., Grondin Y., Millet E.J., Bartos A., Bortoni M., dos Santos C.O.G., Trevino-Villarreal H.J., Sepulveda R., Rogers R. In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes. Proteome Sci. 2018;16:7. doi: 10.1186/s12953-018-0132-x. PubMed DOI PMC

Morgan N.E., Cutrona M.B., Simpson J.C. Multitasking Rab Proteins in Autophagy and Membrane Trafficking: A Focus on Rab33b. Int. J. Mol. Sci. 2019;20:3916. doi: 10.3390/ijms20163916. PubMed DOI PMC

Takahashi T., Minami S., Tsuchiya Y., Tajima K., Sakai N., Suga K., Hisanaga S., Ohbayashi N., Fukuda M., Kawahara H. Cytoplasmic control of Rab family small GTPases through BAG6. EMBO Rep. 2019;20:e46794. doi: 10.15252/embr.201846794. PubMed DOI PMC

Ceresa B.P. Regulation of EGFR endocytic trafficking by rab proteins. Histol. Histopathol. 2006;21:987–993. PubMed

Hermle T., Schneider R., Schapiro D., Braun D.A., van der Ven A.T., Warejko J.K., Daga A., Widmeier E., Nakayama M., Jobst-Schwan T., et al. GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome. J. Am. Soc. Nephrol. 2018;29:2123–2138. doi: 10.1681/ASN.2017121312. PubMed DOI PMC

Escobar-Henriques M., Anton V. Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion. Int. J. Mol. Sci. 2020;21:6841. doi: 10.3390/ijms21186841. PubMed DOI PMC

D’Aloia A., Berruti G., Costa B., Schiller C., Ambrosini R., Pastori V., Martegani E., Ceriani M. RalGPS2 is involved in tunneling nanotubes formation in 5637 bladder cancer cells. Exp. Cell Res. 2018;362:349–361. doi: 10.1016/j.yexcr.2017.11.036. PubMed DOI

Rebhun J.F., Chen H.S., Quilliam L.A. Identification and characterization of a new family of guanine nucleotide exchange factors for the Ras-related GTPase Ral. J. Biol. Chem. 2000;275:13406–13410. doi: 10.1074/jbc.C000085200. PubMed DOI

Cornish J., Owen D., Mott H.R. RLIP76: A Structural and Functional Triumvirate. Cancers. 2021;13:2206. doi: 10.3390/cancers13092206. PubMed DOI PMC

Herlevsen M.C., Theodorescu D. Mass spectroscopic phosphoprotein mapping of Ral binding protein 1 (RalBP1/Rip1/RLIP76) Biochem. Biophys. Res. Commun. 2007;362:56–62. doi: 10.1016/j.bbrc.2007.07.163. PubMed DOI PMC

Koo T.H., Eipper B.A., Donaldson J.G. Arf6 recruits the Rac GEF Kalirin to the plasma membrane facilitating Rac activation. BMC Cell Biol. 2007;8:29. doi: 10.1186/1471-2121-8-29. PubMed DOI PMC

Osmani N., Peglion F., Chavrier P., Etienne-Manneville S. Cdc42 localization and cell polarity depend on membrane traffic. J. Cell Biol. 2010;191:1261–1269. doi: 10.1083/jcb.201003091. PubMed DOI PMC

Conner S.D., Schmid S.L. Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis. J. Cell Biol. 2002;156:921–929. doi: 10.1083/jcb.200108123. PubMed DOI PMC

Lee D.W., Wu X.F., Eisenberg E., Greene L.E. Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis. J. Cell Sci. 2006;119:3502–3512. doi: 10.1242/jcs.03092. PubMed DOI

Ricotta D., Conner S.D., Schmid S.L., von Figura K., Honing S. Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. J. Cell Biol. 2002;156:791–795. doi: 10.1083/jcb.200111068. PubMed DOI PMC

Jullien-Flores V., Mahe Y., Mirey G., Leprince C., Meunier-Bisceuil B., Sorkin A., Camonis J.H. RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: Involvement of the Ral pathway in receptor endocytosis. J. Cell Sci. 2000;113:2837–2844. doi: 10.1242/jcs.113.16.2837. PubMed DOI

Fillatre J., Delacour D., Van Hove L., Bagarre T., Houssin N., Soulika M., Veitia R.A., Moreau J. Dynamics of the subcellular localization of RalBP1/RLIP through the cell cycle: The role of targeting signals and of protein-protein interactions. FASEB J. 2012;26:2164–2174. doi: 10.1096/fj.11-196451. PubMed DOI

Personnic N., Lakisic G., Gouin E., Rousseau A., Gautreau A., Cossart P., Bierne H. A role for Ral GTPase-activating protein subunit beta in mitotic regulation. FEBS J. 2014;281:2977–2989. doi: 10.1111/febs.12836. PubMed DOI

Matunis M.J., Wu J.A., Blobel G. SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex. J. Cell Biol. 1998;140:499–509. doi: 10.1083/jcb.140.3.499. PubMed DOI PMC

Dorr A., Pierre S., Zhang D.D., Henke M., Holland S., Scholich K. MYCBP2 Is a Guanosine Exchange Factor for Ran Protein and Determines Its Localization in Neurons of Dorsal Root Ganglia. J. Biol. Chem. 2015;290:25620–25635. doi: 10.1074/jbc.M115.646901. PubMed DOI PMC

Yoon S.O., Shin S., Liu Y., Ballif B.A., Woo M.S., Gygi S.P., Blenis J. Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport. Mol. Cell. 2008;29:362–375. doi: 10.1016/j.molcel.2007.12.024. PubMed DOI PMC

Bischoff F.R., Klebe C., Kretschmer J., Wittinghofer A., Ponstingl H. RanGAP1 induced GTPase activity of nuclear Ras-related Ran. Proc. Natl. Acad. Sci. USA. 1994;91:2587–2591. doi: 10.1073/pnas.91.7.2587. PubMed DOI PMC

He Y.J., Yang Z.G., Zhao C.S., Xiao Z.H., Gong Y., Li Y.Y., Chen Y.Q., Du Y.T., Feng D.Y., Altman A., et al. T-cell receptor (TCR) signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-theta-mediated phosphorylation of RanGAP1. eLife. 2021;10:e67123. doi: 10.7554/eLife.67123. PubMed DOI PMC

Sanz-Garcia M., Lopez-Sanchez I., Lazo P.A. Proteomics Identification of Nuclear Ran GTPase as an Inhibitor of Human VRK1 and VRK2 (Vaccinia-related Kinase) Activities. Mol. Cell. Prot. 2008;7:2199–2214. doi: 10.1074/mcp.M700586-MCP200. PubMed DOI PMC

Radha V., Mitra A., Dayma K., Sasikumar K. Signalling to actin: Role of C3G, a multitasking guanine-nucleotide-exchange factor. Biosci. Rep. 2011;31:231–244. doi: 10.1042/BSR20100094. PubMed DOI

Chen X., Shibata A.C.E., Hendi A., Kurashina M., Fortes E., Weilinger N.L., MacVicar B.A., Murakoshi H., Mizumoto K. Rap2 and TNIK control Plexin-dependent tiled synaptic innervation in C. elegans. eLife. 2018;7:e38801. doi: 10.7554/eLife.38801. PubMed DOI PMC

Smolen G.A., Schott B.J., Stewart R.A., Diederichs S., Muir B., Provencher H.L., Look A.T., Sgroi D.C., Peterson R.T., Haber D.A. A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors. Gen. Dev. 2007;21:2131–2136. doi: 10.1101/gad.1561507. PubMed DOI PMC

Sequera C., Manzano S., Guerrero C., Porras A. How Rap and its GEFs control liver physiology and cancer development. C3G alterations in human hepatocarcinoma. Hepatic Oncol. 2018;5:HEP05. doi: 10.2217/hep-2017-0026. PubMed DOI PMC

Baker M.J., Pan D.X., Welch H.C.E. Small GTPases and their guanine-nucleotide exchange factors and GTPase-activating proteins in neutrophil recruitment. Curr. Opin. Hematol. 2016;23:44–54. doi: 10.1097/MOH.0000000000000199. PubMed DOI

Schultess J., Danielewski O., Smolenski A.P. Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets. Blood. 2005;105:3185–3192. doi: 10.1182/blood-2004-09-3605. PubMed DOI

Park Y.G., Zhao X.H., Lesueur F., Lowy D.R., Lancaster M., Pharoah P., Qian X.L., Hunter K.W. Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nat. Genet. 2005;37:1055–1062. doi: 10.1038/ng1635. PubMed DOI PMC

Rosano L., Cianfrocca R., Masi S., Spinella F., Di Castro V., Biroccio A., Salvati E., Nicotra M.R., Natali P.G., Bagnato A. beta-Arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis. Proc. Natl. Acad. Sci. USA. 2009;106:2806–2811. doi: 10.1073/pnas.0807158106. PubMed DOI PMC

Eisemann T., McCauley M., Langelier M.F., Gupta K., Roy S., Van Duyne G.D., Pascal J.M. Tankyrase-1 Ankyrin Repeats Form an Adaptable Binding Platform for Targets of ADP-Ribose Modification. Structure. 2016;24:1679–1692. doi: 10.1016/j.str.2016.07.014. PubMed DOI

Murayama M., Tanaka S., Palacino J., Murayama O., Honda T., Sun X.Y., Yasutake K., Nihonmatsu N., Wolozin B., Takashima A. Direct association of presenilin-1 with beta-catenin. FEBS Lett. 1998;433:73–77. doi: 10.1016/S0014-5793(98)00886-2. PubMed DOI

Lee G., Goretsky T., Managlia E., Dirisina R., Singh A.P., Brown J.B., May R., Yang G.Y., Ragheb J.W., Evers B.M., et al. Phosphoinositide 3-Kinase Signaling Mediates beta-Catenin Activation in Intestinal Epithelial Stem and Progenitor Cells in Colitis. Gastroenterology. 2010;139:869–881. doi: 10.1053/j.gastro.2010.05.037. PubMed DOI PMC

Jiang X., Tan J., Li J.S., Kivimaee S., Yang X.J., Zhuang L., Lee P.L., Chan M.T.W., Stanton L.W., Liu E.T., et al. DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications. Cancer Cell. 2008;13:529–541. doi: 10.1016/j.ccr.2008.04.019. PubMed DOI PMC

Sastre-Perona A., Riesco-Eizaguirre G., Zaballos M.A., Santisteban P. beta-catenin signaling is required for RAS-driven thyroid cancer through PI3K activation. Oncotarget. 2016;7:49435–49449. doi: 10.18632/oncotarget.10356. PubMed DOI PMC

Mariotti L., Pollock K., Guettler S. Regulation of Wnt/beta-catenin signalling by tankyrase-dependent poly(ADP-ribosyl) ation and scaffolding. Br. J. Pharmacol. 2017;174:4611–4636. doi: 10.1111/bph.14038. PubMed DOI PMC

Fang D.X., Hawke D., Zheng Y.H., Xia Y., Meisenhelder J., Nika H., Mills G.B., Kobayashi R., Hunter T., Lu Z.M. Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. J. Biol. Chem. 2007;282:11221–11229. doi: 10.1074/jbc.M611871200. PubMed DOI PMC

Bah A., Vernon R.M., Siddiqui Z., Krzeminski M., Muhandiram R., Zhao C., Sonenberg N., Kay L.E., Forman-Kay J.D. Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch. Nature. 2015;519:106–109. doi: 10.1038/nature13999. PubMed DOI

Bah A., Forman-Kay J.D. Modulation of Intrinsically Disordered Protein Function by Post-translational Modifications. J. Biol. Chem. 2016;291:6696–6705. doi: 10.1074/jbc.R115.695056. PubMed DOI PMC

Iakoucheva L.M., Radivojac P., Brown C.J., O’Connor T.R., Sikes J.G., Obradovic Z., Dunker A.K. The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res. 2004;32:1037–1049. doi: 10.1093/nar/gkh253. PubMed DOI PMC

van Gastel J., Hendrickx J.O., Leysen H., Santos-Otte P., Luttrell L.M., Martin B., Maudsley S. beta-Arrestin Based Receptor Signaling Paradigms: Potential Therapeutic Targets for Complex Age-Related Disorders. Front. Pharmacol. 2018;9:1369. doi: 10.3389/fphar.2018.01369. PubMed DOI PMC

Jones B.W., Hinkle P.M. Arrestin binds to different phosphorylated regions of the thyrotropin-releasing hormone receptor with distinct functional consequences. Mol. Pharmacol. 2008;74:195–202. doi: 10.1124/mol.108.045948. PubMed DOI PMC

Oride A., Kanasaki H., Mutiara S., Purwana I.N., Miyazaki K. Activation of extracellular signal-regulated kinase (ERK) and induction of mitogen-activated protein kinase phosphatase 1 (MKP-1) by perifused thyrotropin-releasing hormone (TRH) stimulation in rat pituitary GH3 cells. Mol. Cell. Endocrinol. 2008;296:78–86. doi: 10.1016/j.mce.2008.09.002. PubMed DOI

Sibilski C., Mueller T., Kollipara L., Zahedi R.P., Rapp U.R., Rudel T., Baljuls A. Tyr(728) in the Kinase Domain of the Murine Kinase Suppressor of RAS 1 Regulates Binding and Activation of the Mitogen-activated Protein Kinase Kinase. J. Biol. Chem. 2013;288:35237–35252. doi: 10.1074/jbc.M113.490235. PubMed DOI PMC

McKay M.M., Ritt D.A., Morrison D.K. Signaling dynamics of the KSR1 scaffold complex. Proc. Natl. Acad. Sci. USA. 2009;106:11022–11027. doi: 10.1073/pnas.0901590106. PubMed DOI PMC

Chuang H.C., Wang X.H., Tan T.H. MAP4K Family Kinases in Immunity and Inflammation. Adv. Immunol. 2016;129:277–314. PubMed

Gurevich V.V., Gurevich E.V. Arrestin-mediated signaling: Is there a controversy? World J. Biol. Chem. 2018;9:25–35. doi: 10.4331/wjbc.v9.i3.25. PubMed DOI PMC

Bourquard T., Landomiel F., Reiter E., Crepieux P., Ritchie D.W., Aze J., Poupon A. Unraveling the molecular architecture of a G protein-coupled receptor/beta-arrestin/Erk module complex. Sci. Rep. 2015;5:10760. doi: 10.1038/srep10760. PubMed DOI PMC

Claing A. beta-Arrestins: Modulators of Small GTPase Activation and Function. Mol. Biol. Arrestins. 2013;118:149–174. PubMed

Du R.W., Du R.H., Bu W.G. beta-arrestin 2 mediates the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells. J. Neuroimmune Pharmacol. 2014;9:582–590. doi: 10.1007/s11481-014-9556-y. PubMed DOI

Arakaki A.K.S., Pan W.A., Wedegaertner H., Roca-Mercado I., Chinn L., Gujral T.S., Trejo J.A. α-Arrestin ARRDC3 tumor suppressor function is linked to GPCR-induced TAZ activation and breast cancer metastasis. J. Cell Sci. 2021;134:jcs254888. doi: 10.1242/jcs.254888. PubMed DOI PMC

Wang Y.H., Jue S.F., Maurer R.A. Thyrotropin-releasing hormone stimulates phosphorylation of the epidermal growth factor receptor in GH(3) pituitary cells. Mol. Endocrinol. 2000;14:1328–1337. doi: 10.1210/mend.14.9.0512. PubMed DOI

Luo L.G., Yano N., Luo J.Z.Q. The molecular mechanism of EGF receptor activation in pancreatic beta-cells by thyrotropin-releasing hormone. Am. J. Physiol.-Endocrinol. Metabol. 2006;290:E889–E899. doi: 10.1152/ajpendo.00466.2005. PubMed DOI

Collazos A., Diouf B., Guerineau N.C., Quittau-Prevostel C., Peter M., Coudane F., Hollande F., Joubert D. A spatiotemporally coordinated cascade of protein kinase C activation controls isoform-selective translocation. Mol. Cell. Biol. 2006;26:2247–2261. doi: 10.1128/MCB.26.6.2247-2261.2006. PubMed DOI PMC

Lampe M., Vassilopoulos S., Merrifield C. Clathrin coated pits, plaques and adhesion. J. Struct. Biol. 2016;196:48–56. doi: 10.1016/j.jsb.2016.07.009. PubMed DOI

Thirunarayanan N., Nir E.A., Raaka B.M., Gershengorn M.C. Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice. Neuropsychopharmacology. 2013;38:950–956. doi: 10.1038/npp.2012.256. PubMed DOI PMC

Martinez-Cue C., Rueda N. Signalling Pathways Implicated in Alzheimer’s Disease Neurodegeneration in Individuals with and without Down Syndrome. Int. J. Mol. Sci. 2020;21:6906. doi: 10.3390/ijms21186906. PubMed DOI PMC

Cherubini M., Wade-Martins R. Convergent pathways in Parkinson’s disease. Cell Tissue Res. 2018;373:79–90. doi: 10.1007/s00441-017-2700-2. PubMed DOI PMC

Bohush A., Niewiadomska G., Filipek A. Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease. Int. J. Mol. Sci. 2018;19:2973. doi: 10.3390/ijms19102973. PubMed DOI PMC

Fawdar S., Trotter E.W., Li Y.Y., Stephenson N.L., Hanke F., Marusiak A.A., Edwards Z.C., Ientile S., Waszkowycz B., Miller C.J., et al. Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer. Proc. Natl. Acad. Sci. USA. 2013;110:12426–12431. doi: 10.1073/pnas.1305207110. PubMed DOI PMC

Kahle M.P., Cuevas B.D. Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition. J. Mol. Signal. 2015;10:4. doi: 10.5334/1750-2187-10-4. PubMed DOI PMC

Stark M.S., Woods S.L., Gartside M.G., Bonazzi V.F., Dutton-Regester K., Aoude L.G., Chow D., Sereduk C., Niemi N.M., Tang N.Y., et al. Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing. Nat. Genet. 2012;44:165–169. doi: 10.1038/ng.1041. PubMed DOI PMC

Vaidyanathan H., Opoku-Ansah J., Pastorino S., Renganathan H., Matter M.L., Ramos J.W. ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. Proc. Natl. Acad. Sci. USA. 2007;104:19837–19842. doi: 10.1073/pnas.0704514104. PubMed DOI PMC

Ravindran E., Hu H., Yuzwa S.A., Hernandez-Miranda L.R., Kraemer N., Ninnemann O., Musante L., Boltshauser E., Schindler D., Hubner A., et al. Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation. PLoS Genet. 2017;13:e1006746. doi: 10.1371/journal.pgen.1006746. PubMed DOI PMC

Lee S., Cieply B., Yang Y.Q., Peart N., Glaser C., Chan P., Carstens R.P. Esrp1-Regulated Splicing of Arhgef11 Isoforms Is Required for Epithelial Tight Junction Integrity. Cell Rep. 2018;25:2417–2430. doi: 10.1016/j.celrep.2018.10.097. PubMed DOI PMC

Rykx A., De Kimpe L., Mikhalap S., Vantus T., Seufferlein T., Vandenheede J.R., Van Lint J. Protein kinase D: A family affair. FEBS Lett. 2003;546:81–86. doi: 10.1016/S0014-5793(03)00487-3. PubMed DOI

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