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.
Agrotis
A
A
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
Samuel
M
M
Prapas
G
G
Bobik
A
A
D030201:Activin Receptors, Type I; D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D018076:DNA, Complementary; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D051381:Rats; D011921:Rats, Inbred WKY; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D017931:DNA Primers; D018076:DNA, Complementary; D006133:Growth Substances; 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; C000625843:Tgfbr1 protein, rat