Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex
Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex
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DOI：
10.1242/dev.01045
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发表时间：
2004-05-01
期刊：
影响因子：
4.6
通讯作者：
Smith, JC
中科院分区：
文献类型：
--
作者：
Mercurio, S;Latinkic, B;Smith, JC
结缔组织生长因子(CTGF)是CCN家族分泌蛋白中的一员。CCN家族成员包含四个特征结构域，具有多种功能：与细胞外基质结合，介导细胞黏附、迁移和趋化，调节多肽生长因子的活性。CTGF的许多作用被认为是通过与整合素的结合而介导的，而另一些可能是因为它最近发现的与BMP4和TGFP相互作用的能力。我们用非洲爪哇胚胎证明，CTGF也通过Wnt途径调节信号，这与它与Wnt共同受体低密度脂蛋白受体相关蛋白6(LRP6)结合的能力一致。这种相互作用可能通过CTGF的C末端(CT)结构域发生，该结构域不同于BMP和TGFβ相互作用结构域。我们的结果定义了CTGF的新活性，并增加了细胞在发育、疾病和组织动态平衡中调节生长因子活性的各种途径。
Connective-tissue growth factor (CTGF) is a member of the CCN family of secreted proteins. CCN family members contain four characteristic domains and exhibit multiple activities: they associate with the extracellular matrix, they can mediate cell adhesion, cell migration and chemotaxis, and they can modulate the activities of peptide growth factors. Many of the effects of CTGF are thought to be mediated by binding to integrins, whereas others may be because of its recently identified ability to interact with BMP4 and TGFP. We demonstrate, using Xenopus embryos, that CTGF also regulates signalling through the Wnt pathway, in accord with its ability to bind to the Wnt co-receptor LDL receptor-related protein 6 (LRP6). This interaction is likely to occur through the C-terminal (CT) domain of CTGF, which is distinct from the BMP- and TGFbeta-interacting domain. Our results define new activities of CTGF and add to the variety of routes through which cells regulate growth factor activity in development, disease and tissue homeostasis.