Sci. STKE, 25 January 2000
Immunology Negative Signaling in B Cells
The proteins p62dok and insulin receptor substrate-1 (IRS-1) are structurally very similar, yet, while IRS-1 is involved in stimulating cell proliferation, Yamanashi et al. report that p62dok appears to inhibit proliferation, at least in B cells. When the B-cell receptor (BCR) is stimulated by antigen or is cross-linked, B cells proliferate and secrete antibody. However, when secreted antibody, bound to antigen, induces cross-linking between the BCR and the immunoglobulin receptor FcRIIB, these responses are inhibited. The authors report that B cells from mice lacking p62dok did not exhibit normal inhibition of cell proliferation in response to BCR/FcRIIB cross-linking, suggesting a critical role for p62dok in this feedback inhibition pathway. B cells from p62dok-null mice exhibited higher MAP kinase activation than normal B cells upon BCR/FcRIIB cross-linking, though it is not clear how p62dok might suppress MAP kinase. In normal B cells, p62dok was also tyrosine-phosphorylated upon BCR/FcRIIB cross-linking, and this appears to involve the tyrosine kinase Lyn.
Yamanashi, Y., Tamura, T., Kanamori, T., Yamane, H., Nariuchi, H., Yamamoto, T., and Baltimore, D. (2000) Role of the rasGAP-associated docking protein p62dok in negative regulation of B cell receptor-mediated signaling. Genes Dev. 14:11-16. [Abstract] [Full Text]
Citation: Negative Signaling in B Cells. Sci. STKE 2000, tw4 (2000).
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