The v-Crk oncogene enhances cell survival and induces activation of protein kinase B/Akt

The Journal of Biological Chemistry
J C StamP M van Bergen en Henegouwen

Abstract

The v-Crk oncogene encodes an adaptor protein containing an SH2 domain and an SH3 domain. v-Crk-transformed fibroblast cells display enhanced tyrosine phosphorylation levels, and the v-Crk protein localizes in focal adhesions, suggesting that transformation may be due to enhanced focal complex signaling. Here we investigated the mechanism of transformation and found that v-Crk-transformed NIH 3T3 cells display growth rates and serum requirements similar to control cells. However, v-Crk enhanced survival in conditions of serum starvation. Both an intact SH2 and SH3 domain are required; moreover, SH2 mutants displayed dominant interfering properties, enhancing cell death. Using other cell death-inducing stimuli, it appeared that v-Crk in general inhibits apoptosis and enhances cell survival. In search of the signaling pathways involved, we found that v-Crk-transformed cells show constitutively higher levels of phospho-protein kinase B (PKB)/Akt and PKB/Akt activity, especially in conditions of serum starvation. These data strongly suggest involvement of the phosphatidylinositol 3-kinase/PKB survival pathway in the v-Crk-induced protection against apoptosis. In accordance, inhibition of this pathway by wortmannin or LY924002 reduc...Continue Reading

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Citations

Apr 9, 2005·Experimental Cell Research·Paulo Matos, Peter Jordan
Sep 21, 2002·Molecular and Cellular Biology·Tsuyoshi AkagiHidesaburo Hanafusa
Feb 13, 2002·Molecular and Cellular Biology·Jesse J SmithSally Kornbluth
Aug 29, 2013·International Journal of Biological Sciences·Hyejin OhWoo Keun Song
Dec 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Toshinori IwaharaHidesaburo Hanafusa
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Apr 19, 2006·Proceedings. Biological Sciences·Lilach HadanyMarcus W Feldman
May 19, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Garth PowisD Lynn Kirkpatrick

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