The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor.
Gab1 is a member of the docking/scaffolding protein family which includes IRS-1, IRS-2, c-Cbl, p130(cas), and p62(dok). These proteins contain a variety of protein-protein interaction motifs including multiple tyrosine residues that when phosphorylated can act as binding sites for Src homology 2 (SH2) domain-containing signaling proteins. We show in the ... RAMOS human B cell line that Gab1 is tyrosine-phosphorylated in response to B cell antigen receptor (BCR) engagement. Moreover, tyrosine phosphorylation of Gab1 correlated with the binding of several SH2-containing signaling proteins to Gab1 including Shc, Grb2, phosphatidylinositol 3-kinase, and the SHP-2 tyrosine phosphatase. Far Western analysis showed that the SH2 domains of Shc, SHP-2, and the p85 subunit of phosphatidylinositol 3-kinase could bind directly to tyrosine-phosphorylated Gab1 isolated from activated RAMOS cells. In contrast, the Grb2 SH2 domain did not bind directly to Gab1 but instead to the Shc and SHP-2 associated with Gab1. We also show that Gab1 is present in the membrane-enriched particulate fraction of RAMOS cells and that Gab1/signaling protein complexes are found in this fraction after BCR engagement. Thus, tyrosine-phosphorylated Gab1 may recruit cytosolic signaling proteins to cellular membranes where they can act on membrane-bound targets. This may be a critical step in the activation of multiple BCR signaling pathways.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Binding Sites, GRB2 Adaptor Protein, Humans, Intracellular Signaling Peptides and Proteins, Phosphatidylinositol 3-Kinases, Phosphoproteins, Phosphorylation, Protein Binding, Protein Sorting Signals, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Proteins, Receptors, Antigen, B-Cell, SH2 Domain-Containing Protein Tyrosine Phosphatases, Shc Signaling Adaptor Proteins, Tumor Cells, Cultured, Tyrosine, src Homology Domains
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Binding Sites, GRB2 Adaptor Protein, Humans, Intracellular Signaling Peptides and Proteins, Phosphatidylinositol 3-Kinases, Phosphoproteins, Phosphorylation, Protein Binding, Protein Sorting Signals, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Proteins, Receptors, Antigen, B-Cell, SH2 Domain-Containing Protein Tyrosine Phosphatases, Shc Signaling Adaptor Proteins, Tumor Cells, Cultured, Tyrosine, src Homology Domains
J. Biol. Chem.
Date: Nov. 13, 1998
PubMed ID: 9804835
View in: Pubmed Google Scholar
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