Vascular smooth muscle cells express multiple type I receptors for TGF-beta, activin, and bone morphogenetic proteins

Vascular smooth muscle cells (VSMCs) are known to produce activins, bone morphogenetic proteins and transforming growth factor-betas (TGF-betas). To determine whether these TGF-beta superfamily members exert autocrine effects on VSMCs we examined whether specific type I receptors (ALKs) for such peptides were expressed by the cells. RNA from both quiescent or growth-factor-activated VSMCs was reverse transcribed then cDNAs encoding ALK-2, ALK-3, ALK-5, and ALK-6 were amplified and characterised using specific PCR primers. All four ALK mRNAs were abundantly expressed. The ALK-5 fragment harbored a deletion of 12 nucleotides, removing 4 extracellular amino acids (Gly-Pro-Ser-Val) adjacent to its transmembrane domain. This deletion, which may arise from anomalous splicing of heteronuclear RNA, is likely to influence formation of the ALK-5:type II receptor complex through conformational changes associated with removal of a putative hinge region containing proline. Our finding that multiple ALKs are expressed by VSMCs would account for the multiplicity of effects TGF-beta peptides exert on these cells.