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Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

Oncogene volume 18, pages 7319–7327 (1999)Cite this article

Abstract

Serum Response Factor (SRF) plays a central role in the transcriptional response of mammalian cells to a variety of extracellular signals. It is a key regulator of many cellular early response genes which are believed to be involved in cell growth, differentiation, and development. The mechanism by which SRF activates transcription in response to mitogenic agents has been extensively studied, however, less is known about regulation of the SRF gene itself. Previously, we identified distinct regulatory elements in the SRF promoter that play a role in activation, including an ETS domain binding site, an overlapping Sp1/Egr-1 binding site, and two SRF binding sites. We further showed that serum induces the SRF gene by a mechanism that requires an intact SRF binding site, also termed a CArG box. In the present study we demonstrate that in response to stimulation by cells by lysophosphatidic acid (LPA) or whole serum, the SRF promoter is upregulated by a bipartite pathway that requires both an Sp1 factor binding site and the CArG motifs for maximal stimulation. The CArG box-dependent component of this pathway is targeted by Rho mediated signals, and the Sp1 binding site dependent component is targeted by Ras mediated signals.

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Acknowledgements

We thank Vaughn Jackson for critical reading of the manuscript. We thank J Silvio Gutkind for his kind gift of Rho-family inhibitory plasmids, and Robert Tjian for the Gal4 – Sp1 expression plasmid. This work was supported in part by the following to RP Misra: an American Cancer Society Institutional Seed Grant Award from the Medical College of Wisconsin Cancer Center; a Grant-in-Aid from the American Heart Association, Wisconsin Division; a Shannon Award (R55 GM/OD51856) and a FIRST Award (R29 NS36256) from the National Institutes of Health.

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  1. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, 53226, Wisconsin, WI, USA

    Jeffrey A Spencer & Ravi P Misra

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  1. Jeffrey A Spencer
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Spencer, J., Misra, R. Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals. Oncogene 18, 7319–7327 (1999). https://doi.org/10.1038/sj.onc.1203121

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