Caveolin-1 regulates transforming growth factor (TGF)-β/SMAD signaling through an interaction with the TGF-β type I receptor
Caveolin-1 regulates transforming growth factor (TGF)-β/SMAD signaling through an interaction with the TGF-β type I receptor
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DOI：
10.1074/jbc.m008340200
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发表时间：
2001-03-02
影响因子：
4.8
通讯作者：
Lisanti, MP
中科院分区：
文献类型：
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作者：
Razani, B;Zhang, XL;Lisanti, MP
转化生长因子-β（TGF-β）信号传导通过I型和II型丝氨酸/苏氨酸激酶受体及其下游SMAD效应物的合作从细胞膜进行到细胞核。虽然已经描述了影响TGF-β介导的事件的各种调节蛋白，但对质膜水平上的受体相互作用知之甚少。Caveolae是富含胆固醇的膜微区，其沿着其标记蛋白Caveolin-1（Cav-1），已经涉及某些信号事件的区室化和调节。在这里，我们证明了TGF-β级联反应的特定组分与小窝中的小窝蛋白-1相关，并且Cav-1与I型TGF-β受体相互作用。此外，Cav-1能够抑制TGF-β介导的Smad-2磷酸化和随后的下游事件。我们将I型TGF-β受体相互作用定位于Cav-1的支架结构域，并表明它发生在生理相关的时间范围内，可迅速抑制TGF-β受体复合物引发的信号传导。
Transforming growth factor-beta (TGF-beta) signaling proceeds from the cell membrane to the nucleus through the cooperation of the type I and II serine/threonine kinase receptors and their downstream SMAD effecters. Although various regulatory proteins affecting TGF-beta -mediated events have been described, relatively little is known about receptor interactions at the level of the plasma membrane. Caveolae are cholesterol-rich membrane microdomains that, along with their marker protein caveolin-1 (Cav-1), have been implicated in the compartmentalization and regulation of certain signaling events. Here, we demonstrate that specific components of the TGF-beta cascade are associated with caveolin-1 in caveolae and that Cav-1 interacts with the Type I TGF-beta receptor. Additionally, Cav-1 is able to suppress TGF-beta -mediated phosphorylation of Smad-2 and subsequent downstream events. We localize the Type I TGF-beta receptor interaction to the scaffolding domain of Cav-1 and show that it occurs in a physiologically relevant time frame, acting to rapidly dampen signaling initiated by the TGF-beta receptor complex.