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A Three-Body Problem

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Science  01 Sep 2000:
Vol. 289, Issue 5484, pp. 1435
DOI: 10.1126/science.289.5484.1435c

Hedgehog (Hh) is a secreted signaling protein that regulates tissue patterning during Drosophila development by binding to Patched (Ptc), its cell surface receptor. Signal transmission is accommodated by another cell surface protein called Smoothened (Smo), and it is thought that a preformed complex of Ptc and Smo inhibits Smo-mediated signaling; that is, when Hh binds to Ptc, a conformational change would relieve Ptc-mediated repression of Smo.

Now, in support of an indirect interaction, Denef et al. propose that, in the absence of Hh, Ptc promotes dephosphorylation of Smo through a type 2A protein phosphatase. Binding of Hh to Ptc causes a decrease in the amount of cell-surface Ptc, which may deactivate this phosphatase, resulting in increased phosphorylation of Smo and localization to the cell surface for signal transduction. — LDC

Cell102, 521 (2000).

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