Four isoforms of serum response factor that increase or inhibit smooth-muscle-specific promoter activity.
Serum response factor (SRF) is a key transcriptional activator of the c-fos gene and of muscle-specific gene expression. We have identified four forms of the SRF coding sequence, SRF-L (the previously identified form), SRF-M, SRF-S and SRF-I, that are produced by alternative splicing. The new forms of SRF lack regions of the C-terminal transactivation domain by splicing out of exon 5 (SRF-M), exons 4 and 5 (SRF-S) and exons 3, 4 and 5 (SRF-I). SRF-M is expressed at similar levels to SRF-L in differentiated vascular smooth-muscle cells and skeletal-muscle cells, whereas SRF-L is the predominant form in many other tissues. SRF-S expression is restricted to vascular smooth muscle and SRF-I expression is restricted to the embryo. Transfection of SRF-L and SRF-M into C(2)C(12) cells showed that both forms are transactivators of the promoter of the smooth-muscle-specific gene SM22alpha, whereas SRF-I acted as a dominant negative form of SRF.
Kemp
P R
PR
Section of Cardiovascular Biology, Department of Biochemistry, University of Cambridge, The Downing Site, Tennis Court Road, Cambridge CB2 1QW, U.K. pk@mole.bio.cam.ac.uk
Metcalfe
J C
JC
D017398:Alternative Splicing; D000818:Animals; D018236:Carcinoma, Embryonal; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D026362:Serum Response Factor; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D026362:Serum Response Factor; C058992:Tagln protein, mouse; C051615:transgelin