Phosphorylation of cyclin dependent kinase 4 on tyrosine 17 is mediated by Src family kinases.

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Citation

Martin NG, McAndrew PC, Eve PD, Garrett MD

Phosphorylation of cyclin dependent kinase 4 on tyrosine 17 is mediated by Src family kinases.

FEBS J. 2008 Jun;275(12):3099-109. doi: 10.1111/j.1742-4658.2008.06463.x. Epub 2008 May 8.

PubMed ID
18479465 [ View in PubMed
]
Abstract

Cyclin dependent kinase 4 is a key regulator of the cell cycle and its activity is frequently deregulated in cancer. The activity of cyclin dependent kinase 4 is controlled by multiple mechanisms, including phosphorylation of tyrosine 17. This site is equivalent to tyrosine 15 of cyclin dependent kinase 1, which undergoes inhibitory phosphorylation by WEE1 and MYT1; however, the kinases that phosphorylate cyclin dependent kinase 4 on tyrosine 17 are still unknown. In the present study, we generated a phosphospecific antibody to the tyrosine 17-phosphorylated form of cyclin dependent kinase 4, and showed that this site is phosphorylated to a low level in asynchronously proliferating HCT116 cells. We purified tyrosine 17 kinases from HeLa cells and found that the Src family non-receptor tyrosine kinase C-YES contributes a large fraction of the tyrosine 17 kinase activity in HeLa lysates. C-YES also phosphorylated cyclin dependent kinase 4 when transfected into HCT116 cells, and treatment of cells with Src family kinase inhibitors blocked the tyrosine 17 phosphorylation of cyclin dependent kinase 4. Taken together, the results obtained in the present study provide the first evidence that Src family kinases, but not WEE1 or MYT1, phosphorylate cyclin dependent kinase 4 on tyrosine 17, and help to resolve how the phosphorylation of this site is regulated.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Tyrosine-protein kinase YesP07947Details