Alternative splicing within the TGF-beta type I receptor gene (ALK-5) generates two major functional isoforms in vascular smooth muscle cells.
We have identified in rat vascular smooth muscle cells (SMCs) the simultaneous expression of two TGF-beta type I receptor (ALK-5) cDNAs, occurring as a consequence of alternate usage of AG splice acceptor motifs separated by 12 nucleotides located at an intron-exon junction. When translated the resultant full length proteins differ from each other only by the in-frame presence or absence of Gly-Pro-Phe-Ser residues adjacent to their transmembrane domain. Stable expression of these alternate ALK-5 isoforms in ALK-5-deficient cells demonstrated that both were competent in signaling TGF-beta-induced growth inhibition and gene transcription, but with an apparently distinct potency. Our data suggest that alternate splicing within the ALK-5 gene is an important mechanism whereby SMCs may regulate their response to TGF-beta.
Agrotis
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Cell Biology Laboratory, Baker Medical Research Institute, Alfred Hospital, Prahran, Vic., Australia. alex.agrotis@baker.edu.au
Condron
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Bobik
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D030201:Activin Receptors, Type I; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta; D001483:Base Sequence; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D005091:Exons / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625843:Tgfbr1 protein, rat