Vascular Smooth Muscle Cells Express Multiple Type I Receptors for TGF-β,Activin, and Bone Morphogenetic Proteins ☆

Vascular Smooth Muscle Cells Express Multiple Type I Receptors for TGF-β,Activin, and Bone Morphogenetic Proteins ☆
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血管平滑肌细胞表达多种 TGF-β、激活素和骨形态发生蛋白的 I 型受体 ☆

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发表时间:
1996
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通讯作者:
A. Bobik
A. Bobik
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作者:
A. Agrotis;M. Samuel;G. Prapas;A. Bobik

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血管平滑肌细胞(VSMC)能产生激活素、骨形态发生蛋白和转化生长因子-β(TGF-βs)。为了确定这些TGF-β超家族成员是否对VSMC发挥自分泌作用,我们检查了这些肽的特异性I型受体(ALK)是否由细胞表达。对来自静止或生长因子激活的VSMC的RNA进行逆转录,然后使用特异性PCR引物扩增编码ALK-2、ALK-3、ALK-5和ALK-6的cDNA并进行表征。所有四种ALK mRNA均大量表达。ALK-5片段含有12个核苷酸的缺失,去除了与其跨膜结构域相邻的4个胞外氨基酸(Gly-Pro-Ser-Val)。这种缺失可能由异源RNA的异常剪接引起,可能通过与去除含脯氨酸的假定铰链区相关的构象变化影响ALK-5:II型受体复合物的形成。我们发现VSMC表达多种ALK,这将解释TGF-β肽对这些细胞发挥的多种作用。
Abstract Vascular smooth muscle cells (VSMCs) are known to produce activins, bone morphogenetic proteins and transforming growth factor-βs (TGF-βs). To determine whether these TGF-β 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-β peptides exert on these cells.