![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Genes and Development
Vol. 11, No. 17,
pp. 2250-2258,
September 1, 1997
Department of Biological Sciences, Columbia University,
New York, New York 10027 USA
The secreted Drosophila Hedgehog (Hh) protein induces
transcription of specific genes by an unknown mechanism that requires the serpentine transmembrane protein Smoothened (Smo) and the transcription factor Cubitus interruptus (Ci). Protein kinase A (PKA)
has been implicated in the mechanism of Hh signal transduction because
it acts to repress Hh target genes in imaginal disc cells that express
Ci. Changes in Ci protein levels, detected by an antibody that
recognizes an epitope in the carboxy-terminal half of Ci, have been
suggested to mediate the positive effects of Hh and the negative
effects of PKA on Hh target gene expression in imaginal discs. Here we
show that PKA inhibition, like Hh, leads to increased
"carboxy-terminal" Ci staining and Hh target gene expression in
embryos. In addition, we find that Hh and Smo can stimulate target gene
expression at constant Ci levels and that increased PKA activity can
induce ectopic Hh target gene expression in a manner that requires Smo
and Ci activities but does not involve changes in Ci protein
concentration. This suggests a branching pathway of Hh signal
transduction downstream of Smo and that PKA exerts opposite effects on
the two branches. Finally we show that Hh signaling in embryos does not
depend on cAMP-dependent regulation of PKA activity.
[Key Words: Protein kinase A; Hedgehog; Cubitus interruptus; Drosophila; signal transduction; development]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  N. A. Riobo, B. Saucy, C. DiLizio, and D. R. Manning Activation of heterotrimeric G proteins by Smoothened PNAS, August 15, 2006; 103(33): 12607 - 12612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhou, S. Apionishev, and D. Kalderon The Contributions of Protein Kinase A and Smoothened Phosphorylation to Hedgehog Signal Transduction in Drosophila melanogaster Genetics, August 1, 2006; 173(4): 2049 - 2062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zhang, E. H. Williams, Y. Guo, L. Lum, and P. A. Beachy Inaugural Article: Extensive phosphorylation of Smoothened in Hedgehog pathway activation PNAS, December 28, 2004; 101(52): 17900 - 17907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Jia, C. Tong, and J. Jiang Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail Genes & Dev., November 1, 2003; 17(21): 2709 - 2720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Fu and N. E. Baker Deciphering synergistic and redundant roles of Hedgehog, Decapentaplegic and Delta that drive the wave of differentiation in Drosophila eye development Development, November 1, 2003; 130(21): 5229 - 5239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kawakami and N. Nakanishi The role of an endogenous PKA inhibitor, PKI{alpha}, in organizing left-right axis formation Development, July 1, 2001; 128(13): 2509 - 2515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Kiger Jr. and C. O'Shea Genetic Evidence for a Protein Kinase A/Cubitus Interruptus Complex That Facilitates Processing of Cubitus Interruptus in Drosophila Genetics, July 1, 2001; 158(3): 1157 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Wolfgang, A. Hoskote, I. J. H. Roberts, S. Jackson, and M. Forte Genetic Analysis of the Drosophila Gs{{alpha}} Gene Genetics, July 1, 2001; 158(3): 1189 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mohanty, S. Lee, N. Yadava, M. J. Dealy, R. S. Johnson, and R. A. Firtel Regulated protein degradation controls PKA function and cell-type differentiation in Dictyostelium Genes & Dev., June 1, 2001; 15(11): 1435 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Methot and K Basler Suppressor of fused opposes hedgehog signal transduction by impeding nuclear accumulation of the activator form of Cubitus interruptus Development, January 9, 2000; 127(18): 4001 - 4010. [Abstract] [PDF]
|
|
|
|
 |
|
 W Norris, C Neyt, P. Ingham, and P. Currie Slow muscle induction by Hedgehog signalling in vitro J. Cell Sci., January 8, 2000; 113(15): 2695 - 2703. [Abstract] [PDF]
|
|
|
|
|
|
Q. Wang and R. Holmgren Nuclear import of cubitus interruptus is regulated by hedgehog via a mechanism distinct from Ci stabilization and Ci activation Development, January 7, 2000; 127(14): 3131 - 3139. [Abstract] [PDF]
|
|
|
|
|
|
T Suzuki and K Saigo Transcriptional regulation of atonal required for Drosophila larval eye development by concerted action of eyes absent, sine oculis and hedgehog signaling independent of fused kinase and cubitus interruptus Development, January 4, 2000; 127(7): 1531 - 1540. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Borjigin, J. Deng, M. M. Wang, X. Li, S. Blackshaw, and S. H. Snyder Circadian Rhythm of Patched1 Transcription in the Pineal Regulated by Adrenergic Stimulation and cAMP J. Biol. Chem., December 3, 1999; 274(49): 35012 - 35015. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wang, B. Wang, and J. Jiang Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus Genes & Dev., November 1, 1999; 13(21): 2828 - 2837. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Kiger , Jr., J. L. Eklund, S. H. Younger, and C. J. O'Kane Transgenic Inhibitors Identify Two Roles for Protein Kinase A in Drosophila Development Genetics, May 1, 1999; 152(1): 281 - 290. [Abstract] [Full Text]
|
|
|
|
|
|
P. Dai, H. Akimaru, Y. Tanaka, T. Maekawa, M. Nakafuku, and S. Ishii Sonic Hedgehog-induced Activation of the Gli1 Promoter Is Mediated by GLI3 J. Biol. Chem., March 19, 1999; 274(12): 8143 - 8152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Price and D Kalderon Proteolysis of cubitus interruptus in Drosophila requires phosphorylation by protein kinase A Development, January 10, 1999; 126(19): 4331 - 4339. [Abstract] [PDF]
|
|
|
|
|
|
Y Chen, J. Cardinaux, R. Goodman, and S. Smolik Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling Development, January 8, 1999; 126(16): 3607 - 3616. [Abstract] [PDF]
|
|
|
|
|
|
K. Lewis, G Drossopoulou, I. Paton, D. Morrice, K. Robertson, D. Burt, P. Ingham, and C Tickle Expression of ptc and gli genes in talpid3 suggests bifurcation in Shh pathway Development, January 6, 1999; 126(11): 2397 - 2407. [Abstract] [PDF]
|
|
|
|
|
|
A Ruiz i Altaba Gli proteins encode context-dependent positive and negative functions: implications for development and disease Development, January 6, 1999; 126(14): 3205 - 3216. [Abstract] [PDF]
|
|
|
|
|
|
Y. Chen, N. Gallaher, R. H. Goodman, and S. M. Smolik Protein kinase A directly regulates the activity and proteolysis of cubitus interruptus PNAS, March 3, 1998; 95(5): 2349 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Yasukawa, S Mohanty, and R. Firtel Identification and analysis of a gene that is essential for morphogenesis and prespore cell differentiation in Dictyostelium Development, January 7, 1998; 125(14): 2565 - 2576. [Abstract] [PDF]
|
|
|
|
|
|
D Lessing and R Nusse Expression of wingless in the Drosophila embryo: a conserved cis-acting element lacking conserved Ci-binding sites is required for patched-mediated repression Development, January 4, 1998; 125(8): 1469 - 1476. [Abstract] [PDF]
|
|
|
|
|
|
M. A. Stegman, J. E. Vallance, G. Elangovan, J. Sosinski, Y. Cheng, and D. J. Robbins Identification of a Tetrameric Hedgehog Signaling Complex J. Biol. Chem., July 14, 2000; 275(29): 21809 - 21812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kim, K. Jee, D. Kim, H. Koh, and J. Chung Cyclic AMP Inhibits Akt Activity by Blocking the Membrane Localization of PDK1 J. Biol. Chem., April 13, 2001; 276(16): 12864 - 12870. [Abstract] [Full Text] [PDF]
|
|
