PMID- 10409506
OWN - NLM
STAT- MEDLINE
DCOM- 19991008
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 126
IP  - 16
DP  - 1999 Aug
TI  - Mutants of cubitus interruptus that are independent of PKA regulation are
      independent of hedgehog signaling.
PG  - 3607-16
AB  - Hedgehog (HH) is an important morphogen involved in pattern formation during
      Drosophila embryogenesis and disc development. cubitus interruptus (ci) encodes a
      transcription factor responsible for transducing the hh signal in the nucleus and
      activating hh target gene expression. Previous studies have shown that CI exists 
      in two forms: a 75 kDa proteolytic repressor form and a 155 kDa activator form.
      The ratio of these forms, which is regulated positively by hh signaling and
      negatively by PKA activity, determines the on/off status of hh target gene
      expression. In this paper, we demonstrate that the exogenous expression of CI
      that is mutant for four consensus PKA sites [CI(m1-4)], causes ectopic expression
      of wingless (wg) in vivo and a phenotype consistent with wg overexpression.
      Expression of CI(m1-4), but not CI(wt), can rescue the hh mutant phenotype and
      restore wg expression in hh mutant embryos. When PKA activity is suppressed by
      expressing a dominant negative PKA mutant, the exogenous expression of CI(wt)
      results in overexpression of wg and lethality in embryogenesis, defects that are 
      similar to those caused by the exogenous expression of CI(m1-4). In addition, we 
      demonstrate that, in cell culture, the mutation of any one of the three
      serine-containing PKA sites abolishes the proteolytic processing of CI. We also
      show that PKA directly phosphorylates the four consensus phosphorylation sites in
      vitro. Taken together, our results suggest that positive hh and negative PKA
      regulation of wg gene expression converge on the regulation of CI
      phosphorylation.
FAU - Chen, Y
AU  - Chen Y
AD  - Vollum Institute and Department of Cell and Developmental Biology L-215, Oregon
      Health Sciences University, Portland, OR 97201, USA.
FAU - Cardinaux, J R
AU  - Cardinaux JR
FAU - Goodman, R H
AU  - Goodman RH
FAU - Smolik, S M
AU  - Smolik SM
LA  - eng
GR  - DK44239/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Insect Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (ci protein, Drosophila)
RN  - 149291-21-4 (hh protein, Drosophila)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Binding Sites
MH  - *Body Patterning
MH  - Consensus Sequence
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - DNA-Binding Proteins/chemistry/*genetics/*metabolism
MH  - *Drosophila Proteins
MH  - Drosophila melanogaster/*embryology/genetics
MH  - Hedgehog Proteins
MH  - Insect Proteins/genetics/*physiology
MH  - Morphogenesis
MH  - Peptide Mapping
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Transcription Factors
MH  - Transfection
MH  - Zinc Fingers
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
AID - 10.1242/dev.126.16.3607 [doi]
PST - ppublish
SO  - Development. 1999 Aug;126(16):3607-16. doi: 10.1242/dev.126.16.3607.