Association of Src-family kinase Lyn with B-cell antigen receptor.
Antigen is thought to cross-link membrane-bound immunoglobulins (Igs) of B cells, causing proliferation and differentiation or the inhibition of growth. Compelling evidence suggests that protein-tyrosine phosphorylation is involved in signal transduction for cell proliferation and differentiation. Indeed cross-linking of membrane-bound IgM (mIgM) induced a rapid increase in tyrosine phosphorylation of at least 10 distinct proteins in B cells. The Src-family protein tyrosine kinase Lyn (p56lyn and p53lyn) is expressed preferentially in B cells. The Lyn protein and its kinase activity could be coimmunoprecipitated with both IgM and IgD from detergent lysates. Cross-linking of membrane-bound IgM with antibody induced down-regulation of the Lyn protein. From these data we concluded that Lyn is physically associated with mIgs. Further evidence showed that cross-linking of mIgM induced rapid increase in the kinase activity of Lyn and association of Lyn with 85-kDa noncatalytic subunit of phosphatidylinositol 3-kinase. Thus, Lyn is likely to participate in B-cell antigen receptor-mediated signaling. As a novel signaling molecule downstream of Lyn, we identified src homology 3-containing, transcription factor-like molecule p75HS1.
Yamamoto
T
T
Institute of Medical Science, University of Tokyo, Japan.
Yamanashi
Y
Y
Toyoshima
K
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002454:Cell Differentiation; D007075:Immunoglobulin M / Q000378:metabolism; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D014443:Tyrosine; D019061:src-Family Kinases
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; C061909:HCLS1 protein, human; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases