C-terminal Src kinase (CSK) is a major negative regulator of Src family tyrosine kinases (SFKs) that play critical roles in immunoreceptor signaling. CSK is brought in contiguity to the plasma membrane-bound SFKs via binding to transmembrane adaptor PAG, also known as CSK-binding protein. The recent finding that PAG can function as a positive regulator of the high-affinity IgE receptor (FcεRI)-mediated mast cell signaling suggested that PAG and CSK have some non-overlapping regulatory functions in mast cell activation. To determine the regulatory roles of CSK in FcεRI signaling, we derived bone marrow-derived mast cells (BMMCs) with reduced or enhanced expression of CSK from wild-type (WT) or PAG knockout (KO) mice and analyzed their FcεRI-mediated activation events. We found that in contrast to PAG-KO cells, antigen-activated BMMCs with CSK knockdown (KD) exhibited significantly higher degranulation, calcium response, and tyrosine phosphorylation of FcεRI, SYK, and phospholipase C. Interestingly, FcεRI-mediated events in BMMCs with PAG-KO were restored upon CSK silencing. BMMCs with CSK-KD/PAG-KO resembled BMMCs with CSK-KD alone. Unexpectedly, cells with CSK-KD showed reduced kinase activity of LYN and decreased phosphorylation of transcription factor STAT5. This was accompanied by impaired production of proinflammatory cytokines and chemokines in antigen-activated cells. In line with this, BMMCs with CSK-KD exhibited enhanced phosphorylation of protein phosphatase SHP-1, which provides a negative feedback loop for regulating phosphorylation of STAT5 and LYN kinase activity. Furthermore, we found that in WT BMMCs SHP-1 forms complexes containing LYN, CSK, and STAT5. Altogether, our data demonstrate that in FcεRI-activated mast cells CSK is a negative regulator of degranulation and chemotaxis, but a positive regulator of adhesion to fibronectin and production of proinflammatory cytokines. Some of these pathways are not dependent on the presence of PAG.

• Keywords
• C-terminal Src kinase, LYN, SHP-1, STAT5, cytokines, degranulation, mast cell, phosphoprotein associated with glycosphingolipid-enriched microdomains,
• MeSH
• Analysis of Variance MeSH
• Bone Marrow Cells physiology   MeSH
• CSK Tyrosine-Protein Kinase MeSH
• Cytokines metabolism   MeSH
• Cell Degranulation MeSH
• Fibronectins metabolism   MeSH
• Phosphoproteins metabolism   MeSH
• Phosphorylation MeSH
• Genetic Vectors MeSH
• HEK293 Cells MeSH
• Humans MeSH
• Mast Cells physiology   MeSH
• Membrane Proteins metabolism   MeSH
• Intercellular Signaling Peptides and Proteins MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Receptors, IgE metabolism   MeSH
• Signal Transduction immunology   MeSH
• src-Family Kinases metabolism   physiology   MeSH
• STAT5 Transcription Factor metabolism   MeSH
• Tyrosine metabolism   MeSH
• Protein Tyrosine Phosphatase, Non-Receptor Type 6 metabolism   MeSH
• Calcium metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CSK Tyrosine-Protein Kinase MeSH
• CSK protein, human MeSH Browser
• Cytokines MeSH
• Fibronectins MeSH
• Phosphoproteins MeSH
• lyn protein-tyrosine kinase MeSH Browser
• Membrane Proteins MeSH
• Intercellular Signaling Peptides and Proteins MeSH
• Pag protein, mouse MeSH Browser
• Pag1 protein, mouse MeSH Browser
• Ptpn6 protein, mouse MeSH Browser
• Receptors, IgE MeSH
• src-Family Kinases MeSH
• STAT5 Transcription Factor MeSH
• Tyrosine MeSH
• Protein Tyrosine Phosphatase, Non-Receptor Type 6 MeSH
• Calcium MeSH

Mast cells play crucial roles in both innate and adaptive arms of the immune system. Along with basophils, mast cells are essential effector cells for allergic inflammation that causes asthma, allergic rhinitis, food allergy and atopic dermatitis. Mast cells are usually increased in inflammatory sites of allergy and, upon activation, release various chemical, lipid, peptide and protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)-mediated activation of these cells is a central event to trigger allergic reactions, innumerable studies have been conducted on how these cells are activated through cross-linking of the high-affinity IgE receptor (FcεRI). Development of mature mast cells from their progenitor cells is under the influence of several growth factors, of which the stem cell factor (SCF) seems to be the most important. Therefore, how SCF induces mast cell development and activation via its receptor, KIT, has been studied extensively, including a cross-talk between KIT and FcεRI signaling pathways. Although our understanding of the signaling mechanisms of the FcεRI and KIT pathways is far from complete, pharmaceutical applications of the knowledge about these pathways are underway. This review will focus on recent progresses in FcεRI and KIT signaling and chemotaxis.

• Keywords
• Chemotaxis, IgE receptor, KIT receptor, Mast cell, Plasma membrane, Signal transduction,
• MeSH
• Chemotaxis * drug effects   MeSH
• Humans MeSH
• Mast Cells cytology   drug effects   MeSH
• Signal Transduction * drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Research Support, N.I.H., Extramural MeSH

The transmembrane adaptor protein PAG/CBP (here, PAG) is expressed in multiple cell types. Tyrosine-phosphorylated PAG serves as an anchor for C-terminal SRC kinase, an inhibitor of SRC-family kinases. The role of PAG as a negative regulator of immunoreceptor signaling has been examined in several model systems, but no functions in vivo have been determined. Here, we examined the activation of bone marrow-derived mast cells (BMMCs) with PAG knockout and PAG knockdown and the corresponding controls. Our data show that PAG-deficient BMMCs exhibit impaired antigen-induced degranulation, extracellular calcium uptake, tyrosine phosphorylation of several key signaling proteins (including the high-affinity IgE receptor subunits, spleen tyrosine kinase, and phospholipase C), production of several cytokines and chemokines, and chemotaxis. The enzymatic activities of the LYN and FYN kinases were increased in nonactivated cells, suggesting the involvement of a LYN- and/or a FYN-dependent negative regulatory loop. When BMMCs from PAG-knockout mice were activated via the KIT receptor, enhanced degranulation and tyrosine phosphorylation of the receptor were observed. In vivo experiments showed that PAG is a positive regulator of passive systemic anaphylaxis. The combined data indicate that PAG can function as both a positive and a negative regulator of mast cell signaling, depending upon the signaling pathway involved.

• MeSH
• Anaphylaxis genetics   MeSH
• Bone Marrow Cells metabolism   physiology   MeSH
• CSK Tyrosine-Protein Kinase MeSH
• Cell Degranulation MeSH
• Type C Phospholipases metabolism   MeSH
• Phosphoproteins genetics   MeSH
• Phosphorylation MeSH
• Intracellular Signaling Peptides and Proteins metabolism   MeSH
• Syk Kinase MeSH
• RNA, Small Interfering MeSH
• Mast Cells metabolism   physiology   MeSH
• Membrane Proteins genetics   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Proto-Oncogene Proteins c-fyn biosynthesis   MeSH
• Proto-Oncogene Proteins c-kit metabolism   MeSH
• Receptors, IgE metabolism   MeSH
• RNA Interference MeSH
• Signal Transduction MeSH
• src-Family Kinases biosynthesis   metabolism   MeSH
• Protein-Tyrosine Kinases metabolism   MeSH
• Calcium metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CSK Tyrosine-Protein Kinase MeSH
• Type C Phospholipases MeSH
• Phosphoproteins MeSH
• Fyn protein, mouse MeSH Browser
• Intracellular Signaling Peptides and Proteins MeSH
• Syk Kinase MeSH
• lyn protein-tyrosine kinase MeSH Browser
• RNA, Small Interfering MeSH
• Membrane Proteins MeSH
• Pag1 protein, mouse MeSH Browser
• Proto-Oncogene Proteins c-fyn MeSH
• Proto-Oncogene Proteins c-kit MeSH
• Receptors, IgE MeSH
• src-Family Kinases MeSH
• Syk protein, mouse MeSH Browser
• Protein-Tyrosine Kinases MeSH
• Calcium MeSH

In spite of a comprehensive understanding of the schematics of T cell receptor (TCR) signaling, the mechanisms regulating compartmentalization of signaling molecules, their transient interactions, and rearrangement of membrane structures initiated upon TCR engagement remain an outstanding problem. These gaps in our knowledge are exemplified by recent data demonstrating that TCR triggering is largely dependent on a preactivated pool of Lck concentrated in T cells in a specific type of membrane microdomains. Our current model posits that in resting T cells all critical components of TCR triggering machinery including TCR/CD3, Lck, Fyn, CD45, PAG, and LAT are associated with distinct types of lipid-based microdomains which represent the smallest structural and functional units of membrane confinement able to negatively control enzymatic activities and substrate availability that is required for the initiation of TCR signaling. In addition, the microdomains based segregation spatially limits the interaction of components of TCR triggering machinery prior to the onset of TCR signaling and allows their rapid communication and signal amplification after TCR engagement, via the process of their coalescence. Microdomains mediated compartmentalization thus represents an essential membrane organizing principle in resting T cells. The integration of these structural and functional aspects of signaling into a unified model of TCR triggering will require a deeper understanding of membrane biology, novel interdisciplinary approaches and the generation of specific reagents. We believe that the fully integrated model of TCR signaling must be based on membrane structural network which provides a proper environment for regulatory processes controlling TCR triggering.

• Keywords
• Fyn, Lck, TCR triggering, compartmentalization, heavy and light DRMs, membrane microdomains, spatio-temporal regulation,
• Publication type
• Journal Article MeSH

BACKGROUND: The importance of membrane compartmentalization into specific membrane microdomains has been shown in many biological processes such as immunoreceptor signaling, membrane trafficking, pathogen infection, and tumor progression. Microdomains like lipid rafts, caveolae and tetraspanin enriched microdomains are relatively resistant to solubilization by some detergents. Large detergent-resistant membrane fragments (DRMs) resulting from such membrane solubilization can be conveniently isolated by density gradient ultracentrifugation or gel filtration. Recently, we described a novel type of raft-like membrane microdomains producing, upon detergent Brij98 solubilization, "heavy DRMs" and containing a number of functionally relevant proteins. Transmembrane adaptor protein LAX is a typical "heavy raft" protein. The present study was designed to identify the molecular determinants targeting LAX-derived constructs to heavy rafts. METHODOLOGY/PRINCIPAL FINDINGS: We prepared several constructs encoding chimeric proteins containing various informative segments of the LAX sequence and evaluated their effects on targeting to heavy rafts. Replacement of the polybasic membrane-proximal part of LAX by CD3ε-derived membrane-proximal part had no effect on LAX solubilization. Similarly, the membrane-proximal part of LAX, when introduced into non-raft protein CD25 did not change CD25 detergent solubility. These results indicated that membrane-proximal part of LAX is not important for LAX targeting to heavy rafts. On the other hand, the replacement of transmembrane part of CD25 by the transmembrane part of LAX resulted in targeting into heavy rafts. We also show that LAX is not S-acylated, thus palmitoylation is not involved in LAX targeting to heavy rafts. Also, covalent dimerization was excluded as a cause of targeting into heavy rafts. CONCLUSIONS/SIGNIFICANCE: We identified the transmembrane domain of LAX as a first motif targeting transmembrane protein constructs to detergent-resistant heavy rafts, a novel type of membrane microdomains containing a number of physiologically important proteins.

• MeSH
• Adaptor Proteins, Vesicular Transport chemistry   genetics   metabolism   MeSH
• Cell Line MeSH
• Protein Interaction Domains and Motifs MeSH
• Humans MeSH
• Membrane Microdomains genetics   metabolism   MeSH
• Protein Multimerization MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Vesicular Transport MeSH
• LAX1 protein, human MeSH Browser

Formation of the immunological synapse between an antigen-presenting cell (APC) and a T cell leads to signal generation in both cells involved. In T cells, the lipid raft-associated transmembrane adaptor protein LAT plays a central role. Its phosphorylation is a crucial step in signal propagation, including the calcium response and mitogen-activated protein kinase activation, and largely depends on its association with the SLP76 adaptor protein. Here we report the discovery of a new palmitoylated transmembrane adaptor protein, termed SCIMP. SCIMP is expressed in B cells and other professional APCs and is localized in the immunological synapse due to its association with tetraspanin-enriched microdomains. In B cells, it is constitutively associated with Lyn kinase and becomes tyrosine phosphorylated after major histocompatibility complex type II (MHC-II) stimulation. When phosphorylated, SCIMP binds to the SLP65 adaptor protein and also to the inhibitory kinase Csk. While the association with SLP65 initiates the downstream signaling cascades, Csk binding functions as a negative regulatory loop. The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions.

• MeSH
• Adaptor Proteins, Signal Transducing chemistry   metabolism   MeSH
• Lymphocyte Activation MeSH
• Antigen-Presenting Cells immunology   MeSH
• B-Lymphocytes immunology   metabolism   MeSH
• CSK Tyrosine-Protein Kinase MeSH
• Phosphoproteins metabolism   MeSH
• HEK293 Cells MeSH
• Immunological Synapses chemistry   MeSH
• Humans MeSH
• RNA, Small Interfering MeSH
• Membrane Microdomains chemistry   metabolism   MeSH
• Membrane Proteins chemistry   genetics   immunology   metabolism   MeSH
• Histocompatibility Antigens Class II immunology   metabolism   MeSH
• Mitogen-Activated Protein Kinases metabolism   MeSH
• Molecular Sequence Data MeSH
• Antigen Presentation MeSH
• RNA Interference MeSH
• Amino Acid Sequence MeSH
• Signal Transduction MeSH
• src-Family Kinases metabolism   MeSH
• src Homology Domains MeSH
• T-Lymphocytes immunology   MeSH
• Protein-Tyrosine Kinases chemistry   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing MeSH
• B cell linker protein MeSH Browser
• CSK Tyrosine-Protein Kinase MeSH
• CSK protein, human MeSH Browser
• Phosphoproteins MeSH
• lyn protein-tyrosine kinase MeSH Browser
• RNA, Small Interfering MeSH
• Membrane Proteins MeSH
• Histocompatibility Antigens Class II MeSH
• Mitogen-Activated Protein Kinases MeSH
• SCIMP protein, human MeSH Browser
• src-Family Kinases MeSH
• SLP-76 signal Transducing adaptor proteins MeSH Browser
• Protein-Tyrosine Kinases MeSH

Transmembrane adaptor proteins (TRAPs) are important organizers and regulators of immunoreceptor-mediated signaling. A bioinformatic search revealed several potential novel TRAPs, including a highly conserved protein, proline rich 7 (PRR7), previously described as a component of the PSD-95/N-methyl-d-aspartate receptor protein complex in postsynaptic densities (PSD) of rat neurons. Our data demonstrate that PRR7 is weakly expressed in other tissues but is readily up-regulated in activated human peripheral blood lymphocytes. Transient overexpression of PRR7 in Jurkat T cell line led to gradual apoptotic death dependent on the WW domain binding motif surrounding Tyr-166 in the intracellular part of PRR7. To circumvent the pro-apoptotic effect of PRR7, we generated Jurkat clones with inducible expression of PRR7 (J-iPRR7). In these cells acute induction of PRR7 expression had a dual effect. It resulted in up-regulation of the transcription factor c-Jun and the activation marker CD69 as well as enhanced production of IL-2 after phorbol 12-myristate 13-acetate (PMA) and ionomycin treatment. On the other hand, expression of PRR7 inhibited general tyrosine phosphorylation and calcium influx after T cell receptor cross-linking by antibodies. Moreover, we found PRR7 constitutively tyrosine-phosphorylated and associated with Src. Collectively, these data indicate that PRR7 is a potential regulator of signaling and apoptosis in activated T cells.

• MeSH
• Adaptor Proteins, Signal Transducing biosynthesis   genetics   immunology   MeSH
• Amino Acid Motifs MeSH
• Apoptosis drug effects   physiology   MeSH
• Caco-2 Cells MeSH
• Antigens, CD biosynthesis   genetics   immunology   MeSH
• Antigens, Differentiation, T-Lymphocyte biosynthesis   genetics   immunology   MeSH
• Phosphorylation drug effects   physiology   MeSH
• HEK293 Cells MeSH
• Interleukin-2 biosynthesis   genetics   immunology   MeSH
• Ionophores pharmacology   MeSH
• Ionomycin pharmacology   MeSH
• Jurkat Cells MeSH
• Carcinogens pharmacology   MeSH
• Rats MeSH
• Lectins, C-Type biosynthesis   genetics   immunology   MeSH
• Humans MeSH
• Proto-Oncogene Proteins c-jun genetics   immunology   metabolism   MeSH
• Receptors, Antigen, T-Cell genetics   immunology   metabolism   MeSH
• Gene Expression Regulation physiology   MeSH
• T-Lymphocytes immunology   metabolism   MeSH
• Protein Structure, Tertiary MeSH
• Tetradecanoylphorbol Acetate pharmacology   MeSH
• U937 Cells MeSH
• Calcium Signaling drug effects   physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing MeSH
• Antigens, CD MeSH
• CD69 antigen MeSH Browser
• Antigens, Differentiation, T-Lymphocyte MeSH
• IL2 protein, human MeSH Browser
• Interleukin-2 MeSH
• Ionophores MeSH
• Ionomycin MeSH
• Carcinogens MeSH
• Lectins, C-Type MeSH
• Proto-Oncogene Proteins c-jun MeSH
• Receptors, Antigen, T-Cell MeSH
• Tetradecanoylphorbol Acetate MeSH

Aggregation of the high-affinity IgE receptor (FcεRI) initiates a cascade of signaling events leading to release of preformed inflammatory and allergy mediators and de novo synthesis and secretion of cytokines and other compounds. The first biochemically well defined step of this signaling cascade is tyrosine phosphorylation of the FcεRI subunits by Src family kinase Lyn, followed by recruitment and activation of spleen tyrosine kinase (Syk). Activity of Syk is decisive for the formation of multicomponent signaling assemblies, the signalosomes, in the vicinity of the receptors. Formation of the signalosomes is dependent on the presence of transmembrane adaptor proteins (TRAPs). These proteins are characterized by a short extracellular domain, a single transmembrane domain, and a cytoplasmic tail with various motifs serving as anchors for cytoplasmic signaling molecules. In mast cells five TRAPs have been identified [linker for activation of T cells (LAT), non-T cell activation linker (NTAL), linker for activation of X cells (LAX), phosphoprotein associated with glycosphingolipid-enriched membrane microdomains (PAG), and growth factor receptor-bound protein 2 (Grb2)-binding adaptor protein, transmembrane (GAPT)]; engagement of four of them (LAT, NTAL, LAX, and PAG) in FcεRI signaling has been documented. Here we discuss recent progress in the understanding of how TRAPs affect FcεRI-mediated mast cell signaling. The combined data indicate that individual TRAPs have irreplaceable roles in important signaling events such as calcium response, degranulation, cytokines production, and chemotaxis.

• Keywords
• IgE receptor, LAT/LAT1, LAX, NTAL/Lab/LAT2, PAG/Cbp, mast cells, plasma membrane, transmembrane adaptor proteins,
• Publication type
• Journal Article MeSH

Lymphocyte membrane rafts contain molecules critical for immunoreceptor signaling. Here, we report identification of a new raft-associated adaptor protein LIME (Lck-interacting molecule) expressed predominantly in T lymphocytes. LIME becomes tyrosine phosphorylated after cross-linking of the CD4 or CD8 coreceptors. Phospho-LIME associates with the Src family kinase Lck and its negative regulator, Csk. Ectopic expression of LIME in Jurkat T cells results in an increase of Csk in lipid rafts, increased phosphorylation of Lck and higher Ca2+ response to CD3 stimulation. Thus, LIME appears to be involved in regulation of T cell activation by coreceptors.

• MeSH
• Adaptor Proteins, Vesicular Transport genetics   immunology   metabolism   MeSH
• CD4 Antigens immunology   MeSH
• CD8 Antigens immunology   MeSH
• CSK Tyrosine-Protein Kinase MeSH
• Databases, Protein MeSH
• Phosphorylation MeSH
• DNA, Complementary MeSH
• Humans MeSH
• Membrane Microdomains immunology   MeSH
• Molecular Sequence Data MeSH
• Amino Acid Sequence MeSH
• src-Family Kinases MeSH
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck) metabolism   MeSH
• Protein-Tyrosine Kinases metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Vesicular Transport MeSH
• CD4 Antigens MeSH
• CD8 Antigens MeSH
• CSK Tyrosine-Protein Kinase MeSH
• CSK protein, human MeSH Browser
• DNA, Complementary MeSH
• Lck-interacting protein, mouse MeSH Browser
• src-Family Kinases MeSH
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck) MeSH
• Protein-Tyrosine Kinases MeSH

A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non-T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcgamma- and Fc epsilon -receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cbl. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non-T cells.

• MeSH
• Adaptor Proteins, Signal Transducing * MeSH
• Lymphocyte Activation MeSH
• B-Lymphocytes immunology   metabolism   MeSH
• Cell Line MeSH
• Killer Cells, Natural immunology   metabolism   MeSH
• Phosphoproteins chemistry   genetics   isolation & purification   metabolism   MeSH
• Phosphorylation MeSH
• Humans MeSH
• Lymphoid Tissue cytology   metabolism   MeSH
• Membrane Microdomains chemistry   metabolism   MeSH
• Membrane Proteins chemistry   genetics   isolation & purification   metabolism   MeSH
• Molecular Sequence Data MeSH
• Monocytes immunology   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Proteins * MeSH
• Receptors, Antigen, B-Cell metabolism   MeSH
• Receptors, Fc metabolism   MeSH
• Receptors, IgE metabolism   MeSH
• Receptors, IgG metabolism   MeSH
• Amino Acid Sequence MeSH
• Signal Transduction * MeSH
• T-Lymphocytes immunology   metabolism   MeSH
• Carrier Proteins chemistry   genetics   isolation & purification   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing * MeSH
• Phosphoproteins MeSH
• LAT protein, human MeSH Browser
• Lat protein, mouse MeSH Browser
• LAT2 protein, human MeSH Browser
• LAT2 protein, mouse MeSH Browser
• Membrane Proteins MeSH
• Proteins * MeSH
• Receptors, Antigen, B-Cell MeSH
• Receptors, Fc MeSH
• Receptors, IgE MeSH
• Receptors, IgG MeSH
• Carrier Proteins MeSH