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Science 15 September 1995:
Vol. 269. no. 5230, pp. 1567 - 1569
DOI: 10.1126/science.7545311

Articles

Science, Vol 269, Issue 5230, 1567-1569
Copyright © 1995 by American Association for the Advancement of Science


articles

Requirement for Src family protein tyrosine kinases in G2 for fibroblast cell division

S Roche, S Fumagalli, and SA Courtneidge

Institut National de la Sante et de la Recherche Medicale (INSERM) faculte de Pharmacie, Montpellier, France.

The protein tyrosine kinase c-Src is transiently activated at the transition from the G2 phase to mitosis in the cell cycle of mammalian fibroblasts. Fyn and Yes, the other members of the Src family present in fibroblasts, were also found to be activated at mitosis. In cells microinjected with a neutralizing antibody specific for Src, Fyn, and Yes (anti-cst.1) during G2, cell division was inhibited by 75 percent. The block occurred before nuclear envelope breakdown. Antibodies specific 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 only functional Src family kinase was Src itself. Thus, Src family kinases and proteins associating with their SH2 domains are required for entry into mitosis.


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