Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen receptors, causes proliferation and differentiation of B cells or inhibition of their growth.The receptor-mediated signaling involves tyrosine phosphorylation of cellular proteins and rapid activation of Src-like kinases. The amino acid sequences of five proteolytic peptides of p75, a major substrate of protein-tyrosine kinase(s) in the signaling, showed that p75 is the human HS1 gene product. The HS1 gene is expressed specifically in hematopoietic cells and encodes p75HSl, which carries both helix-turhelix and Src homology 3 motifs. p75HSl showed rapid tyrosine phosphorylation and association with a Src-like kinase, Lyn, after crosslinking of membrane-bound IgM. Thus, p75HS1 may be an important substrate of Lyn and possibly other protein-tyrosine kinases upon B-cell antigen receptor-mediated signaling.Membrane-bound immunoglobulin (mIg) forms an antigen receptor complex on the plasma membrane of B cells with at least two transmembrane proteins, MB-1 and B29 (1-3). In general, crosslinking of the receptor complex of resting B cells by antigens or antibodies to the immunoglobulins activates B cells to enter the G1 phase of the cell cycle, in which they become susceptible to proliferative signals provided by helper T cells. These responses are preceded by phosphatidylinositol turnover, activation of phospholipase C, and Ca2+ mobilization, which are apparently dependent on the functions of a GTP-binding protein(s), protein-tyrosine kinase(s), and protein-tyrosine-phosphatase(s) (1, 2). The tyrosine phosphorylation of proteins after mlg crosslinking is thought to be an initial intracellular signaling event. As mlg, MB-1, and B29 carry no catalytic domain, the receptor must regulate protein-tyrosine kinase(s) as an intracytoplasmic signal transducer(s) (1-3).Src-like kinases are intracytoplasmic protein-tyrosine kinases of 55-60 kDa that are thought to be localized on the inner part of the plasma membrane via myristic acid (4, 5).

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