The members of the Src-family kinases are Src, Lyn, Fyn, Yes, Hck, Lck, Fgr, Blk, and Yrk. Each of these have a common structure consisting of an unique domain at the N-terminal, followed by SH3, SH2 and tyrosine kinase domains.
In immume cells, the Src-family kinases play roles as critical regulators of a large number of intracellular signaling pathways, including integrin signaling pathway. Integrins are major cellular receptor that mediate cell to cell and cell to substratum interactions.
The intracellular protein kinase Lyn participates both positively and negatively in B cell, mast cell, platelet and myeloid cell signaling. Lyn is the predominantly expressed Src-family kinase in B cells and its positive role is done through phosphorylation of the Ig_ and Ig_ subunits of B cell receptor. Genetic deletion of Lyn results in autoimmunity, renal disease and premature mortality in mice, and generation of hyperactive Lyn results in the same phenotype, revealing the importance of the balance of Lyn signaling. |