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Alternative splicing within the TGF-beta type I receptor gene (ALK-5) generates two major functional isoforms in
A Agrotis1, M Condron, A Bobik
1Cell Biology Laboratory, Baker Medical Research Institute, Alfred Hospital, Prahran, Vic., Australia. alex.agrotis@baker.edu.au
Abstract:
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.