Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling.

Abstract:

:Gli proteins are transcriptional effectors of the Hedgehog (Hh) pathway in both normal development and cancer. We describe a program of multisite phosphorylation that regulates the conversion of Gli proteins into transcriptional activators. In the absence of Hh ligands, Gli activity is restrained by the direct phosphorylation of six conserved serine residues by protein kinase A (PKA), a master negative regulator of the Hh pathway. Activation of signaling leads to a global remodeling of the Gli phosphorylation landscape: the PKA target sites become dephosphorylated, while a second cluster of sites undergoes phosphorylation. The pattern of Gli phosphorylation can regulate Gli transcriptional activity in a graded fashion, suggesting a phosphorylation-based mechanism for how a gradient of Hh signaling in a morphogenetic field can be converted into a gradient of transcriptional activity.

journal_name

Cell Rep

journal_title

Cell reports

authors

Niewiadomski P,Kong JH,Ahrends R,Ma Y,Humke EW,Khan S,Teruel MN,Novitch BG,Rohatgi R

doi

10.1016/j.celrep.2013.12.003

subject

Has Abstract

pub_date

2014-01-16 00:00:00

pages

168-181

issue

1

issn

2211-1247

pii

S2211-1247(13)00733-X

journal_volume

6

pub_type

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