Hedgehog Signaling: A Smoothened Conformational Switch
نویسنده
چکیده
An intracellular conformational switch in the serpentine transmembrane protein Smoothened appears to underlie Hedgehog pathway activation. The switch is gated by electrostatic interactions that are regulated by multiple phosphorylations, potentially endowing a dose-dependent response.
منابع مشابه
Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling
In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed...
متن کاملA large complex containing Patched and Smoothened initiates Hedgehog signaling in Drosophila.
Hedgehog acts as an organizer during development. Its signaling involves the receptor Patched, signal transducer Smoothened and a cytoplasmic complex containing the transcription factor Cubitus interruptus tethered to the Smoothened carboxyl tail. Without Hedgehog, Patched represses Smoothened resulting in proteolysis of Cubitus interruptus to its repressor form. With Hedgehog, Patched repressi...
متن کاملThe Hedgehog-induced Smoothened conformational switch assembles a signaling complex that activates Fused by promoting its dimerization and phosphorylation.
Hedgehog (Hh) transduces signal by regulating the subcellular localization and conformational state of the GPCR-like protein Smoothened (Smo) but how Smo relays the signal to cytoplasmic signaling components remains poorly understood. Here, we show that Hh-induced Smo conformational change recruits Costal2 (Cos2)/Fused (Fu) and promotes Fu kinase domain dimerization. We find that induced dimeri...
متن کاملThe role of the desert hedgehog signaling pathway during degeneration and regeneration of peripheral nerves
The desert hedgehog (Dhh) signaling pathway is involved in the development of peripheral nerves (PNs). Dhh-null mice show abnormal neuronal development and perineurial barrier function. As it was previously shown that dhh is mainly expressed in developmental nerves and Sonic hedgehog protein (dhh homologous) has therapeutic effects in neuronal survival, we attempted to investigate the possible ...
متن کاملThe role of the desert hedgehog signaling pathway during degeneration and regeneration of peripheral nerves
The desert hedgehog (Dhh) signaling pathway is involved in the development of peripheral nerves (PNs). Dhh-null mice show abnormal neuronal development and perineurial barrier function. As it was previously shown that dhh is mainly expressed in developmental nerves and Sonic hedgehog protein (dhh homologous) has therapeutic effects in neuronal survival, we attempted to investigate the possible ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Current Biology
دوره 18 شماره
صفحات -
تاریخ انتشار 2008