Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals. Oncogene 1999 Dec 02;18(51):7319-27
Date
12/22/1999Pubmed ID
10602487DOI
10.1038/sj.onc.1203121Scopus ID
2-s2.0-0033518111 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
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.
Author List
Spencer JA, Misra RPAuthor
Ravindra P. Misra PhD Associate Provost, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
3T3 CellsAnimals
Blood Proteins
DNA-Binding Proteins
Early Growth Response Protein 1
Gene Expression Regulation
Immediate-Early Proteins
Mice
Nuclear Proteins
Serum Response Factor
Signal Transduction
Transcription Factors
ras Proteins
