DIFFERENCES IN BINDING OF PI-3-KINASE TO THE SRC-HOMOLOGY DOMAIN-2 AND DOMAIN-3 OF P56 LCK AND P59 FYN TYROSINE KINASES

Two T cell-specific src-family tyrosine kinases, p56 lck (lck) and p59 fyn (fyn), are implicated in regulating PI 3-kinase activity in respo nse to interleukin-2 (IL-2), a cytokine that induces T cell proliferat ion. The src-homology domains 3 (SH3) of src-family kinases can direct ly interact with the PI 3-kinase regulatory subunit p85 and this may b e a mechanism to regulate PI 3-kinase activity. In order to understand the mode of PI 3-kinase activation by the IL-2 receptor, we examined the association of PI 3-kinase to SH2 and SH3 domains of lck and fyn i n IL-2-dependent kit 225 cells. The fyn SH3 domain bound more PI 3-kin ase and its p85 subunit than the lck SH3 domain, while the lck SH2 dom ain bound more PI 3-kinase than the fyn SH2 domain. None of these inte ractions were regulated by IL-2. Low binding of PI 3-kinase to the lck SH3 domain was not observed in IL-2-independent Jurkat T cells. Thus, SH3 and SH2 domains of lck and fyn bound different amounts of PI 3-ki nase, a feature that was dependent on a T cell type, but was not influ enced by IL-2. (C) 1996 Academic Press. Inc.