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Evidence for a role of protein kinase C in FGF signal transduction in the developing chick limb bud.
- Source :
-
Development (Cambridge, England) [Development] 2001 Jul; Vol. 128 (13), pp. 2451-60. - Publication Year :
- 2001
-
Abstract
- In developing limbs, numerous signaling molecules have been identified but less is known about the mechanisms by which such signals direct patterning. We have explored signal transduction pathways in the chicken limb bud. A cDNA encoding RACK1, a protein that binds and stabilizes activated protein kinase C (PKC), was isolated in a screen for genes induced by retinoic acid (RA) in the chick wing bud. Fibroblast growth factor (FGF) also induced RACK1 and such induction of RACK1 expression was accompanied by a significant augmentation in the number of active PKC molecules and an elevation of PKC enzymatic activity. This suggests that PKCs mediate signal transduction in the limb bud. Application of chelerythrine, a potent PKC inhibitor, to the presumptive wing region resulted in buds that did not express sonic hedgehog (Shh) and developed into wings that were severely truncated. This observation suggests that the expression of Shh depends on PKCs. Providing ectopic SHH protein, RA or ZPA grafts overcome the effects of blocking PKC with chelerythrine and resulted in a rescue of the wing morphology. Taken together, these findings suggest that the responsiveness of Shh to FGF is mediated, at least in part, by PKCs.
- Subjects :
- Alkaloids
Animals
Benzophenanthridines
Body Patterning
Chick Embryo
Enzyme Activation
Enzyme Inhibitors pharmacology
Fibroblast Growth Factors genetics
Fibroblast Growth Factors metabolism
Gene Expression
Hedgehog Proteins
Peptides genetics
Peptides metabolism
Phenanthridines pharmacology
Protein Kinase C antagonists & inhibitors
Protein Kinase C metabolism
Proteins metabolism
Receptors for Activated C Kinase
Tretinoin metabolism
Tretinoin pharmacology
Up-Regulation
Wings, Animal embryology
Fibroblast Growth Factors physiology
Limb Buds embryology
Protein Kinase C physiology
Signal Transduction
Trans-Activators
Subjects
Details
- Language :
- English
- ISSN :
- 0950-1991
- Volume :
- 128
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 11493562
- Full Text :
- https://doi.org/10.1242/dev.128.13.2451