Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta.
Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta.
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DOI：
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发表时间：
2002
影响因子：
21.3
通讯作者：
J. Abreu;N. Ketpura;B. Reversade;E. D. De Robertis
中科院分区：
文献类型：
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作者：
J. Abreu;N. Ketpura;B. Reversade;E. D. De Robertis
结缔组织生长因子（CTGF）是一种分泌性蛋白质，参与多种细胞事件，包括血管生成，骨骼生成和伤口愈合。它是CCN分泌蛋白家族的成员，以CTGF、富含半胱氨酸的61（CYR 61）和肾母细胞瘤过表达（NOV）蛋白命名。CTGF或其他CCN蛋白调节细胞信号传导的分子机制尚不清楚。CTGF含有与在脊索蛋白和其他分泌蛋白中发现的那些类似的富含半胱氨酸的结构域（CR），其在某些情况下已被报道用作骨形态发生蛋白（BMP）和TGF-β结合结构域。在这里，我们表明，CTGF直接结合BMP 4和TGF-β 1通过其CR域。CTGF可以通过阻止BMP 4与BMP受体结合来拮抗BMP 4活性，并且对TGF-β 1具有相反的作用，即增强受体结合。这些结果表明，CTGF抑制BMP和激活TGF-β信号通过直接结合在细胞外空间。
Connective-tissue growth factor (CTGF) is a secreted protein implicated in multiple cellular events including angiogenesis, skeletogenesis and wound healing. It is a member of the CCN family of secreted proteins, named after CTGF, cysteine-rich 61 (CYR61), and nephroblastoma overexpressed (NOV) proteins. The molecular mechanism by which CTGF or other CCN proteins regulate cell signalling is not known. CTGF contains a cysteine-rich domain (CR) similar to those found in chordin and other secreted proteins, which in some cases have been reported to function as bone morphogenetic protein (BMP) and TGF-beta binding domains. Here we show that CTGF directly binds BMP4 and TGF-beta 1 through its CR domain. CTGF can antagonize BMP4 activity by preventing its binding to BMP receptors and has the opposite effect, enhancement of receptor binding, on TGF-beta 1. These results show that CTGF inhibits BMP and activates TGF-beta signals by direct binding in the extracellular space.