Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways.

Adapter proteins play a critical role in regulating signals triggered by Ag receptor cross-linking. These small molecules link receptor proximal events with downstream signaling pathways. In this study, we explore the expression and function of the Grb2-related protein of the lymphoid system (GrpL)/Grb2-related adaptor downstream of Shc adapter protein in ...
human B cells. GrpL is expressed in naive B cells and is down-regulated following B cell Ag receptor ligation. By contrast, germinal center and memory B cells express little or no GrpL. Using human B cell lines, we detected constitutive interactions between GrpL and B cell linker protein, Src homology (SH)2 domain-containing leukocyte protein of 76 kDa, hemopoietic progenitor kinase 1, and c-Cbl. The N-terminal SH3 domain of GrpL binds c-Cbl while the C-terminal SH3 domain binds B cell linker protein and SH2 domain-containing leukocyte protein of 76 kDa. Exogenous expression of GrpL in a GrpL-negative B cell line leads to enhanced Ag receptor-induced extracellular signal-related kinase and p38 mitogen-activated protein kinase phosphorylation. Thus, GrpL expression in human B cell subsets appears to regulate Ag receptor-mediated signaling events.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adjuvants, Immunologic, B-Lymphocyte Subsets, Carrier Proteins, Down-Regulation, GRB2 Adaptor Protein, Humans, Interphase, Lymphocyte Activation, Lymphoid Tissue, MAP Kinase Signaling System, Mutagenesis, Site-Directed, Palatine Tonsil, Phosphoproteins, Protein Biosynthesis, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-cbl, Receptors, Antigen, B-Cell, Tumor Cells, Cultured, Ubiquitin-Protein Ligases, src Homology Domains
J. Immunol.
Date: Jan. 01, 2003
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