PMID- 21664578
OWN - NLM
STAT- MEDLINE
DCOM- 20110816
LR  - 20211203
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Print)
IS  - 1534-5807 (Linking)
VI  - 20
IP  - 6
DP  - 2011 Jun 14
TI  - Hedgehog activates fused through phosphorylation to elicit a full spectrum of 
      pathway responses.
PG  - 802-14
LID - 10.1016/j.devcel.2011.04.020 [doi]
AB  - In flies and mammals, extracellular Hedgehog (Hh) molecules alter cell fates and 
      proliferation by regulating the levels and activities of Ci/Gli family 
      transcription factors. How Hh-induced activation of transmembrane Smoothened 
      (Smo) proteins reverses Ci/Gli inhibition by Suppressor of Fused (SuFu) and 
      kinesin family protein (Cos2/Kif7) binding partners is a major unanswered 
      question. Here we show that the Fused (Fu) protein kinase is activated by Smo and 
      Cos2 via Fu- and CK1-dependent phosphorylation. Activated Fu can recapitulate a 
      full Hh response, stabilizing full-length Ci via Cos2 phosphorylation and 
      activating full-length Ci by antagonizing Su(fu) and by other mechanisms. We 
      propose that Smo/Cos2 interactions stimulate Fu autoactivation by concentrating 
      Fu at the membrane. Autoactivation primes Fu for additional CK1-dependent 
      phosphorylation, which further enhances kinase activity. In this model, Smo acts 
      like many transmembrane receptors associated with cytoplasmic kinases, such that 
      pathway activation is mediated by kinase oligomerization and 
      trans-phosphorylation.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Zhou, Qianhe
AU  - Zhou Q
AD  - Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
FAU - Kalderon, Daniel
AU  - Kalderon D
LA  - eng
GR  - R01 GM041815/GM/NIGMS NIH HHS/United States
GR  - R01 GM041815-23/GM/NIGMS NIH HHS/United States
GR  - R01 GM41815/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Transcription Factors)
RN  - 0 (ci protein, Drosophila)
RN  - 0 (cos protein, Drosophila)
RN  - 0 (smo protein, Drosophila)
RN  - EC 2.7.1.- (fu protein, Drosophila)
RN  - EC 2.7.11.1 (Casein Kinase I)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - Animals
MH  - Casein Kinase I/genetics/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Drosophila melanogaster/genetics/growth & development/*metabolism
MH  - Female
MH  - Hedgehog Proteins/genetics/*metabolism
MH  - Immunoenzyme Techniques
MH  - Kinesins/genetics/*metabolism
MH  - Male
MH  - Mutagenesis
MH  - Phosphorylation
MH  - Plasmids
MH  - Polymerase Chain Reaction
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Receptors, G-Protein-Coupled/genetics/*metabolism
MH  - Smoothened Receptor
MH  - Transcription Factors/genetics/*metabolism
PMC - PMC3130625
MID - NIHMS298124
EDAT- 2011/06/15 06:00
MHDA- 2011/08/17 06:00
PMCR- 2012/06/14
CRDT- 2011/06/14 06:00
PHST- 2010/11/16 00:00 [received]
PHST- 2011/01/10 00:00 [revised]
PHST- 2011/04/20 00:00 [accepted]
PHST- 2011/06/14 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2011/08/17 06:00 [medline]
PHST- 2012/06/14 00:00 [pmc-release]
AID - S1534-5807(11)00174-2 [pii]
AID - 10.1016/j.devcel.2011.04.020 [doi]
PST - ppublish
SO  - Dev Cell. 2011 Jun 14;20(6):802-14. doi: 10.1016/j.devcel.2011.04.020.