Lum Lawrence, Zhang Chi, Oh Sekyung, Mann Randall K, von Kessler Doris P, Taipale Jussi, Weis-Garcia Frances, Gong Ruoyu, Wang Baolin, Beachy Philip A
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Mol Cell. 2003 Nov;12(5):1261-74. doi: 10.1016/s1097-2765(03)00426-x.
The seven-transmembrane protein Smoothened (Smo) transduces extracellular activation of the Hedgehog (Hh) pathway by an unknown mechanism to increase transcriptional activity of the latent cytoplasmic transcription factor Ci (Cubitus interruptus). Here, we present evidence that Smo associates directly with a Ci-containing complex that is scaffolded and stabilized by the atypical kinesin, Costal-2 (Cos2). This complex constitutively suppresses pathway activity, but Hh signaling reverses its regulatory effect to promote Ci-mediated transcription. In response to Hh activation of Smo, Cos2 mediates accumulation and phosphorylation of Smo at the membrane as well as phosphorylation of the cytoplasmic components Fu and Su(fu). Positive response of Cos2 to Hh stimulation requires a portion of the Smo cytoplasmic tail and the Cos2 cargo domain, which interacts directly with Smo.
七次跨膜蛋白平滑受体（Smo）通过未知机制转导刺猬信号通路（Hh）的细胞外激活，以增加潜在细胞质转录因子Ci（截断翅脉）的转录活性。在此，我们提供证据表明，Smo直接与包含Ci的复合物结合，该复合物由非典型驱动蛋白Costal-2（Cos2）搭建支架并稳定。这种复合物组成性地抑制信号通路活性，但Hh信号传导会逆转其调节作用以促进Ci介导的转录。响应Hh对Smo的激活，Cos2介导Smo在细胞膜上的积累和磷酸化以及细胞质成分Fu和Su（fu）的磷酸化。Cos2对Hh刺激的阳性反应需要Smo细胞质尾巴的一部分和直接与Smo相互作用的Cos2货物结构域。
