A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity. Mol Cell Biol 1993 Oct;13(10):6260-73
Date
10/01/1993Pubmed ID
8413226Pubmed Central ID
PMC364685DOI
10.1128/mcb.13.10.6260-6273.1993Scopus ID
2-s2.0-0027385031 (requires institutional sign-in at Scopus site) 243 CitationsAbstract
A signaling pathway by which growth factors may induce transcription of the c-fos proto-oncogene has been characterized. Growth factor stimulation of quiescent fibroblasts activates a protein kinase cascade that leads to the rapid and transient phosphorylation of the serum response factor (SRF), a regulator of c-fos transcription. The in vivo kinetics of SRF phosphorylation and dephosphorylation parallel the activation and subsequent repression of c-fos transcription, suggesting that this phosphorylation event plays a critical role in the control of c-fos expression. The ribosomal S6 kinase pp90rsk, a growth factor-inducible kinase, phosphorylates SRF in vitro at serine 103, the site that becomes newly phosphorylated upon growth factor stimulation in vivo. Phosphorylation of serine 103 significantly enhances the affinity and rate with which SRF associates with its binding site, the serum response element, within the c-fos promoter. These results suggest a model in which the growth factor-induced phosphorylation of SRF at serine 103 contributes to the activation of c-fos transcription by facilitating the formation of an active transcription complex at the serum response element.
Author List
Rivera VM, Miranti CK, Misra RP, Ginty DD, Chen RH, Blenis J, Greenberg MEAuthor
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
Antibodies
Base Sequence
Binding Sites
Cell Line
DNA
DNA-Binding Proteins
Epidermal Growth Factor
Humans
Kinetics
Mice
Molecular Sequence Data
Nuclear Proteins
Phosphorylation
Promoter Regions, Genetic
Proto-Oncogene Proteins c-fos
Ribosomal Protein S6
Ribosomal Protein S6 Kinases
Ribosomal Proteins
Serine
Serum Response Factor
Signal Transduction
Transcriptional Activation