• Je něco špatně v tomto záznamu ?

The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases

B. Fafilek, L. Balek, MK. Bosakova, M. Varecha, A. Nita, T. Gregor, I. Gudernova, J. Krenova, S. Ghosh, M. Piskacek, L. Jonatova, NH. Cernohorsky, JT. Zieba, M. Kostas, EM. Haugsten, J. Wesche, C. Erneux, L. Trantirek, D. Krakow, P. Krejci,

. 2018 ; 11 (548) : . [pub] 20180918

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19045242

Grantová podpora
R01 AR066124 NIAMS NIH HHS - United States
R01 AR062651 NIAMS NIH HHS - United States
NV15-33232A MZ0 CEP - Centrální evidence projektů
NV15-34405A MZ0 CEP - Centrální evidence projektů

Sustained activation of extracellular signal-regulated kinase (ERK) drives pathologies caused by mutations in fibroblast growth factor receptors (FGFRs). We previously identified the inositol phosphatase SHIP2 (also known as INPPL1) as an FGFR-interacting protein and a target of the tyrosine kinase activities of FGFR1, FGFR3, and FGFR4. We report that loss of SHIP2 converted FGF-mediated sustained ERK activation into a transient signal and rescued cell phenotypes triggered by pathologic FGFR-ERK signaling. Mutant forms of SHIP2 lacking phosphoinositide phosphatase activity still associated with FGFRs and did not prevent FGF-induced sustained ERK activation, demonstrating that the adaptor rather than the catalytic activity of SHIP2 was required. SHIP2 recruited Src family kinases to the FGFRs, which promoted FGFR-mediated phosphorylation and assembly of protein complexes that relayed signaling to ERK. SHIP2 interacted with FGFRs, was phosphorylated by active FGFRs, and promoted FGFR-ERK signaling at the level of phosphorylation of the adaptor FRS2 and recruitment of the tyrosine phosphatase PTPN11. Thus, SHIP2 is an essential component of canonical FGF-FGFR signal transduction and a potential therapeutic target in FGFR-related disorders.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19045242
003      
CZ-PrNML
005      
20201116111848.0
007      
ta
008      
200109s2018 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1126/scisignal.aap8608 $2 doi
035    __
$a (PubMed)30228226
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Fafilek, Bohumil $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic. International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic.
245    14
$a The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases / $c B. Fafilek, L. Balek, MK. Bosakova, M. Varecha, A. Nita, T. Gregor, I. Gudernova, J. Krenova, S. Ghosh, M. Piskacek, L. Jonatova, NH. Cernohorsky, JT. Zieba, M. Kostas, EM. Haugsten, J. Wesche, C. Erneux, L. Trantirek, D. Krakow, P. Krejci,
520    9_
$a Sustained activation of extracellular signal-regulated kinase (ERK) drives pathologies caused by mutations in fibroblast growth factor receptors (FGFRs). We previously identified the inositol phosphatase SHIP2 (also known as INPPL1) as an FGFR-interacting protein and a target of the tyrosine kinase activities of FGFR1, FGFR3, and FGFR4. We report that loss of SHIP2 converted FGF-mediated sustained ERK activation into a transient signal and rescued cell phenotypes triggered by pathologic FGFR-ERK signaling. Mutant forms of SHIP2 lacking phosphoinositide phosphatase activity still associated with FGFRs and did not prevent FGF-induced sustained ERK activation, demonstrating that the adaptor rather than the catalytic activity of SHIP2 was required. SHIP2 recruited Src family kinases to the FGFRs, which promoted FGFR-mediated phosphorylation and assembly of protein complexes that relayed signaling to ERK. SHIP2 interacted with FGFRs, was phosphorylated by active FGFRs, and promoted FGFR-ERK signaling at the level of phosphorylation of the adaptor FRS2 and recruitment of the tyrosine phosphatase PTPN11. Thus, SHIP2 is an essential component of canonical FGF-FGFR signal transduction and a potential therapeutic target in FGFR-related disorders.
650    _2
$a adaptorové proteiny signální transdukční $x genetika $x metabolismus $7 D048868
650    _2
$a zvířata $7 D000818
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a aktivace enzymů $7 D004789
650    _2
$a extracelulárním signálem regulované MAP kinasy $x genetika $x metabolismus $7 D048049
650    _2
$a HEK293 buňky $7 D057809
650    _2
$a lidé $7 D006801
650    12
$a MAP kinasový signální systém $7 D020935
650    _2
$a membránové proteiny $x genetika $x metabolismus $7 D008565
650    _2
$a fosfatidylinositol-3,4,5-trisfosfát-5-fosfatasy $x genetika $x metabolismus $7 D000072183
650    _2
$a fosforylace $7 D010766
650    _2
$a vazba proteinů $7 D011485
650    _2
$a tyrosinfosfatasa nereceptorového typu 11 $x genetika $x metabolismus $7 D054592
650    _2
$a receptory fibroblastových růstových faktorů $x genetika $x metabolismus $7 D017468
650    _2
$a skupina kinas odvozených od src-genu $x genetika $x metabolismus $7 D019061
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Balek, Lukas $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Bosakova, Michaela Kunova $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic. International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic.
700    1_
$a Varecha, Miroslav $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic. International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic.
700    1_
$a Nita, Alexandru $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Gregor, Tomas $u Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Gudernova, Iva $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Krenova, Jitka $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Ghosh, Somadri $u Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
700    1_
$a Piskacek, Martin $u Department of Pathological Physiology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Jonatova, Lucie $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Cernohorsky, Nicole H $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Zieba, Jennifer T $u Department of Orthopedic Surgery, University of California Los Angeles, CA 90095, USA.
700    1_
$a Kostas, Michal $u Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0379 Oslo, Norway. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.
700    1_
$a Haugsten, Ellen Margrethe $u Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0379 Oslo, Norway. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.
700    1_
$a Wesche, Jørgen $u Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0379 Oslo, Norway. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.
700    1_
$a Erneux, Christophe $u Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
700    1_
$a Trantirek, Lukas $u Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic.
700    1_
$a Krakow, Deborah $u Department of Orthopedic Surgery, University of California Los Angeles, CA 90095, USA. Department of Human Genetics, University of California Los Angeles, CA 90095, USA. Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA.
700    1_
$a Krejci, Pavel $u Department of Biology, Masaryk University, 62500 Brno, Czech Republic. krejcip@med.muni.cz. International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, 60200 Brno, Czech Republic.
773    0_
$w MED00190083 $t Science signaling $x 1937-9145 $g Roč. 11, č. 548 (2018)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/30228226 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20200109 $b ABA008
991    __
$a 20201116111847 $b ABA008
999    __
$a ok $b bmc $g 1483511 $s 1083915
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 11 $c 548 $e 20180918 $i 1937-9145 $m Science signaling $n Sci Signal $x MED00190083
GRA    __
$a R01 AR066124 $p NIAMS NIH HHS $2 United States
GRA    __
$a R01 AR062651 $p NIAMS NIH HHS $2 United States
GRA    __
$a NV15-33232A $p MZ0
GRA    __
$a NV15-34405A $p MZ0
LZP    __
$a Pubmed-20200109

Najít záznam

Citační ukazatele

Možnosti archivace