Medical College of Wisconsin
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The serum response factor is extensively modified by phosphorylation following its synthesis in serum-stimulated fibroblasts. Mol Cell Biol 1991 Sep;11(9):4545-54

Date

09/01/1991

Pubmed ID

1875937

Pubmed Central ID

PMC361330

DOI

10.1128/mcb.11.9.4545-4554.1991

Scopus ID

2-s2.0-0025742603 (requires institutional sign-in at Scopus site)   87 Citations

Abstract

Growth factor regulation of c-fos proto-oncogene transcription is mediated by a 20-bp region of dyad symmetry, termed the serum response element. The inner core of this element binds a 67-kDa phosphoprotein, the serum response factor (SRF), that is thought to play a pivotal role in the c-fos transcriptional response. To investigate the mechanism by which SRF regulates c-fos expression, we generated polyclonal anti-SRF antibodies and used these antibodies to analyze the biochemical properties of SRF. These studies indicate that the synthesis of SRF is transient, occurring within 30 min to 4 h after serum stimulation of quiescent fibroblasts. Newly synthesized SRF is transported to the nucleus, where it is increasingly modified by phosphorylation during progression through the cell cycle. Within 2 h of serum stimulation, differentially modified forms of SRF can be distinguished on the basis of the ability to bind a synthetic serum response element. SRF protein exhibits a half-life of greater than 12 h and is predominantly nuclear, with no change occurring in its localization upon serum stimulation. We find that the induction of SRF synthesis is regulated at the transcriptional level and that cytoplasmic SRF mRNA is transiently expressed with somewhat delayed kinetics compared with c-fos mRNA expression. These features of SRF expression suggest a model whereby newly synthesized SRF functions in the shutoff of c-fos transcription.

Author List

Misra RP, Rivera VM, Wang JM, Fan PD, Greenberg ME

Author

Ravindra P. Misra PhD Associate Provost, Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antibodies
Cell Fractionation
Cell Line
Cell Nucleus
DNA-Binding Proteins
Fibroblasts
Mice
Nuclear Proteins
Phosphorylation
Precipitin Tests
Protein Processing, Post-Translational
Serum Response Factor