Nature 349, 172 - 175 (10 January 1991); doi:10.1038/349172a0

Altered tyrosine 527 phosphorylation and mitotic activation of p60^c-src

Shubha Bagrodia, Isaac Chackalaparampil, Thomas E. Kmiecik^* & David Shalloway^†

Section of Biochemistry, Molecular and Cell Biology and Department of Pathology, Cornell University, Ithaca, New York 14853, USA
^*Present address: Frederick Cancer Research and Development Center, Advanced Bioscience Laboratories, Frederick, Maryland 21702, USA.
^†To whom correspondence should be addressed.

THE tyrosine kinase activity of p60^c-src, the protein product of thec-src gene, increases during mitosis^1,2; this may be important in initiating at least some of the cellular changes that occur during this phase of the cell cycle. Although there is evidence that p60^c-src is phosphorylated at several sites during mitosis, phosphorylation in vitro does not increase its kinase activity^2,3. We now report that the kinase activity of a p60^c-srcmutant with residue tyrosine 527 changed to phenylanine does not change during the cell cycle, suggesting that changes in the phosphorylation state of this residue may be responsible for the activation of p60^c-src at mitosis. Although changes in phosphorylation at Tyr 527 cannot be detected with the wild-type protein we find that phosphorylation at Tyr 527 of a mutant with reduced kinase activity decreases threefold during mitosis. On the basis of these results we suggest that activation of p60^c-src at mitosis results from decreased phosphorylation on Tyr 527, and that p60^c-src may be or may activate the kinase that phosphorylates Tyr 527.

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