VASCULAR SMOOTH-MUSCLE CELLS EXPRESS MULTIPLE TYPE-1 RECEPTORS FOR TGF-BETA, ACTIVIN, AND BONE MORPHOGENETIC PROTEINS

Vascular smooth muscle cells (VSMCs) are known to produce activins, bo ne morphogenetic proteins and transforming growth factor-beta s (TGF-b eta s). To determine whether these TGF-beta superfamily members exert autocrine effects on VSMCs we examined whether specific type I recepto rs (ALKs) for such peptides were expressed by the cells. RNA from both quiescent or growth-factor-activated VSMCs was reverse transcribed th en cDNAs encoding ALK-2, ALK-3, ALK-5, and ALK-6 were amplified and ch aracterised using specific PCR primers. All four ALK mRNAs were abunda ntly expressed. The ALK-5 fragment harbored a deletion of 12 nucleotid es, removing 4 extracellular amino acids (Gly-Pro-Ser-Val) adjacent to its transmembrane domain. This deletion, which may arise from anomalo us splicing of heteronuclear RNA, is likely to influence formation of the ALK-5:type II receptor complex through conformational changes asso ciated with removal of a putative hinge region containing proline. Our finding that multiple ALKs are expressed by VSMCs would account for t he multiplicity of effects TGF-beta peptides exert on these cells. (C) 1996 Academic Press. Inc.