Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56(lck) and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region

Abstract

A previously undescribed 62-kDa protein (p62) that does not contain phosphotyrosine but, nevertheless, binds specifically to the isolated src homology 2 (SH2) domain of p56(lck) has been identified, The additional presence of the unique N-terminal region of p56(lck) prevents p62 binding to the SH2 domain, However, phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56(lck) SH2 domain with p62, Moreover, p62 is associated with a serine/threonine kinase activity and also binds to ras GTPase-activating protein, a negative regulator of the ras signaling pathway. Thus, phosphotyrosine-independent binding of p62 to the p56(lck) SH2 domain appears to provide an alternative pathway for p56(lck) signaling that is regulated by Ser-59 phosphorylation.