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.