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CrkII induces serum response factor activation and cellular transformation through its function in Rho activation

Oncogene volume 22, pages 5946–5957 (2003)Cite this article

Abstract

CrkII belongs to the adaptor protein family that plays a crucial role in signal transduction. In order to better understand the biological functions of CrkII, we focused on the regulation of gene expression by CrkII. Various transcriptional control elements were examined for their activation by CrkII-expression, and we found that CrkII selectively activates the serum response element (SRE), a transcriptional control element of immediate-early genes. This SRE activation induced by CrkII-overexpression was mediated by the serum response factor (SRF) via Rho. Indeed, we confirmed that the amount of activated Rho was increased in the CrkII-expressing cells. Moreover, we showed that when overexpressed, CrkII induces the cellular transformation of NIH 3T3 cells and that a dominant negative mutant of Rho suppresses this transformation, strongly suggesting that activation of Rho is essential for the transforming activity by CrkII. Furthermore, we also found that CrkII and Gα12, a member of the heterotrimeric G proteins, synergistically activates Rho as well as the SRF, and that an SH3 mutant of CrkII can inhibit the Gα12-induced activation of SRF. These results strongly suggest that CrkII is involved in the activation of Rho and SRF by Gα12. Our study provides strong evidence that Rho activation plays a crucial role in CrkII-mediated signals to induce gene expression and cellular transformation.

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Acknowledgements

We thank RN Eisenman, A Hall, H Itoh, S Narumiya, and T Ouchi for providing the plasmids, T Kitamura for Plat-E cells, and M Yutsudo for the facilities of viral infections. We also thank Y Fujitsuka and other members of the Hanafusa laboratory for the technical assistance and helpful discussions. TI thanks S Yamasaki, J Yamauchi, M Yoneda, and T Yamamoto for valuable discussions and encouragement. This work was supported by a grant-in-aid for Specially Promoted Research from the Ministry of Education, Sports, and Culture of Japan.

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  1. Laboratory of Molecular Oncology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka, 565-0874, Japan

    Toshinori Iwahara, Tsuyoshi Akagi, Tomoyuki Shishido & Hidesaburo Hanafusa

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  1. Toshinori Iwahara
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Correspondence to Hidesaburo Hanafusa.

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Iwahara, T., Akagi, T., Shishido, T. et al. CrkII induces serum response factor activation and cellular transformation through its function in Rho activation. Oncogene 22, 5946–5957 (2003). https://doi.org/10.1038/sj.onc.1206633

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