Kawamura Shiho, Hervold Kieran, Ramirez-Weber Felipe-Andrès, Kornberg Thomas B
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
J Biol Chem. 2008 Nov 7;283(45):30964-9. doi: 10.1074/jbc.M806242200. Epub 2008 Sep 2.
Patched (Ptc) is a 12-cross membrane protein that binds the secreted Hedgehog protein. Its regulation of the Hedgehog signaling pathway is critical to normal development and to a number of human diseases. This report analyzes features of sequence similarity and divergence in the Ptc protein family and identifies two subtypes distinguished by novel conserved domains. We used these results to propose a rational basis for classification. We show that one of the conserved sequence regions in the C-terminal domain of Ptch1 is responsible, at least in part, for rapid turnover. This sequence is absent in the stable Ptch2 protein.
patched(Ptc)是一种与分泌型Hedgehog蛋白结合的12次跨膜蛋白。它对Hedgehog信号通路的调控对于正常发育和多种人类疾病至关重要。本报告分析了Ptc蛋白家族的序列相似性和差异特征,并鉴定出由新的保守结构域区分的两种亚型。我们利用这些结果提出了一个合理的分类依据。我们发现,Ptch1 C末端结构域中的一个保守序列区域至少部分负责其快速周转。而稳定的Ptch2蛋白中不存在该序列。