ROLE OF THE AUTOPHOSPHORYLATION SITE ON THE BIOLOGICAL FUNCTION OF PP56(LCK)

Src-family tyrosine kinases act as signaling molecules in a aide array of cellular activation processes. The existence of the various src-fa mily members reflects the requirement for different cell-surface recep tors to transmit cell-type specific intracellular signals. The structu ral basis for the functional specificity of src-kinases is being activ ely investigated. In the present report we have analysed the contribut ion of the area surrounding the autophosphorylation site (located at s ubdomain VII of the catalytic domain) in determining src-kinases activ ity and functional specificity. To this end we analysed the kinase act ivities of the lymphoid src-kinase pp56(lck) and a mutant of pp56(lck) in which this region has been exchanged for the corresponding area of the serine/threonine kinase c-Raf. Our studies indicate that the chan ge at subdomain VII affected the ability of pp56(lck) to phosphorylate physiological substrates. Furthermore, when analysed in T cells, the mutant at subdomain VII failed to induce interleukin-2 production, a s pecific biological function of pp56(lck). Thus, the area surrounding t he autophosphorylation site of pp56(lck) plays a critical role in medi ating its specific biological function.