Stone D M, Hynes M, Armanini M, Swanson T A, Gu Q, Johnson R L, Scott M P, Pennica D, Goddard A, Phillips H, Noll M, Hooper J E, de Sauvage F, Rosenthal A
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA.
Nature. 1996 Nov 14;384(6605):129-34. doi: 10.1038/384129a0.
The protein Sonic hedgehog (Shh) controls patterning and growth during vertebrate development. Here we demonstrate that it binds Patched (vPtc), which has been identified as a tumour-suppressor protein in basal cell carcinoma, with high affinity. We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened (vSmo), and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly. These findings, combined with available genetic evidence from Drosophila, support the hypothesis that Ptc is a receptor for Shh, and that vSmo could be a signalling component that is linked to Ptc.
音猬因子(Shh)蛋白在脊椎动物发育过程中控制模式形成和生长。在此我们证明,它能与在基底细胞癌中被鉴定为肿瘤抑制蛋白的patched(vPtc)高亲和力结合。我们表明,Ptc能与新克隆的果蝇蛋白Smoothened(vSmo)的脊椎动物同源物形成物理复合物,并且vSmo在许多组织中与vPtc共表达,但不直接结合Shh。这些发现,结合来自果蝇的现有遗传学证据,支持了Ptc是Shh的受体,而vSmo可能是与Ptc相关的信号传导成分这一假说。