REQUIREMENT FOR SRC FAMILY PROTEIN-TYROSINE KINASES IN G(2) FOR FIBROBLAST CELL-DIVISION

The protein tyrosine kinase c-Src is transiently activated at the tran sition from the G(2) phase to mitosis in the cell cycle of mammalian f ibroblasts. Fyn and Yes, the other members of the Src family present i n fibroblasts, were also found to be activated at mitosis. In cells mi croinjected with a neutralizing antibody specific for Src, Fyn, and Ye s (anti-cst.1) during G(2), cell division was inhibited by 75 percent. The block occurred before nuclear envelope breakdown. Antibodies spec ific for phosphatidylinositol-3 kinase alpha and phospholipase C-gamma 1 had no effect. Microinjection of the Src homology 2 (SH2) domain of Fyn was also inhibitory. Functional redundancy between members of the Src family was observed; a Src-specific antibody had no effect in NIH 3T3 cells but inhibited cell division in fibroblasts in which the onl y functional Src family kinase was Src itself. Thus, Src family kinase s and proteins associating with their SH2 domains are required for ent ry into mitosis.