PMID- 10557210
OWN - NLM
STAT- MEDLINE
DCOM- 19991222
LR  - 20190605
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 21
DP  - 1999 Nov 1
TI  - Protein kinase A antagonizes Hedgehog signaling by regulating both the activator 
      and repressor forms of Cubitus interruptus.
PG  - 2828-37
AB  - The Hedgehog (Hh) family of secreted proteins controls many aspects of animal
      development. In Drosophila, Hh transduces its signal via Cubitus interruptus
      (Ci), a transcription factor present in two forms: a full-length activator and a 
      carboxy-terminally truncated repressor that is derived from the full-length form 
      by proteolytic processing. The proteolytic processing of Ci is promoted by the
      activities of protein kinase A (PKA) and Slimb, whereas it is inhibited by Hh.
      Here we show that PKA inhibits the activity of the full-length Ci in addition to 
      its role in regulating Ci proteolysis. Whereas Ci processing is blocked in both
      PKA and slimb mutant cells, the accumulated full-length Ci becomes activated only
      in PKA but not in slimb mutant cells. Moreover, PKA inhibits an uncleavable
      activator form of Ci. These observations suggest that PKA regulates the activity 
      of the full-length Ci independent of its proteolytic processing. We also provide 
      evidence that PKA regulates both the proteolytic processing and transcriptional
      activity of Ci by directly phosphorylating Ci. We propose that phosphorylation of
      Ci by PKA has two separable roles: (1) It blocks the transcription activity of
      the full-length activator form of Ci, and (2) it targets Ci for Slimb-mediated
      proteolytic processing to generate the truncated form that functions as a
      repressor.
FAU - Wang, G
AU  - Wang G
AD  - Center for Developmental Biology and Department of Pharmacology, University of
      Texas Southwestern Medical Center, Dallas, Texas 75235-9133, USA.
FAU - Wang, B
AU  - Wang B
FAU - Jiang, J
AU  - Jiang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Insect Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (ci protein, Drosophila)
RN  - 0 (slmb protein, Drosophila)
RN  - 149291-21-4 (hh protein, Drosophila)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - *Drosophila Proteins
MH  - Hedgehog Proteins
MH  - Insect Proteins/*antagonists & inhibitors/genetics/metabolism
MH  - Mutagenesis
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Repressor Proteins/genetics/*metabolism
MH  - *Signal Transduction
MH  - Trans-Activators/genetics/*metabolism
MH  - Transcription Factors
MH  - Transcription, Genetic
MH  - *Ubiquitin-Protein Ligases
PMC - PMC317143
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
AID - 10.1101/gad.13.21.2828 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Nov 1;13(21):2828-37. doi: 10.1101/gad.13.21.2828.