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

A previously undescribed 62-kDa protein (p62) that does not contain ph osphotyrosine but, nevertheless, binds specifically to the isolated sr c homology 2 (SH2) domain of p56(lck) has been identified, The additio nal presence of the unique N-terminal region of p56(lck) prevents p62 binding to the SH2 domain, However, phosphorylation at Ser-59 (or alte rnatively, its mutation to Glu) reverses the inhibition and allows int eraction of the p56(lck) SH2 domain with p62, Moreover, p62 is associa ted with a serine/threonine kinase activity and also binds to ras GTPa se-activating protein, a negative regulator of the ras signaling pathw ay. Thus, phosphotyrosine-independent binding of p62 to the p56(lck) S H2 domain appears to provide an alternative pathway for p56(lck) signa ling that is regulated by Ser-59 phosphorylation.