Modulation of Kit/stem cell factor receptor-induced signaling by protein kinase C
(1994) In Journal of Biological Chemistry 269(34). p.21793-21802- Abstract
- The Kit/stem cell factor receptor (Kit/SCF-R) is a transmembrane tyrosine kinase receptor of importance for the normal development of hemopoietic cells, melanoblasts, and germ cells. We recently reported that protein kinase C (PKC) is involved in a negative feedback loop regulating the Kit/SCF-R by direct phosphorylation on serine residues in the receptor. Inhibition of PKC led to increased SCF-induced tyrosine kinase activity and mitogenicity, but PKC was necessary for SCF-induced motility. In this report we have further examined the modulatory role of PKC on SCF-induced signaling. The ligand-activated Kit/SCF-R associated weakly with GRB2 and induced only little tyrosine phosphorylation of phospholipase C-gamma in porcine aortic... (More)
- The Kit/stem cell factor receptor (Kit/SCF-R) is a transmembrane tyrosine kinase receptor of importance for the normal development of hemopoietic cells, melanoblasts, and germ cells. We recently reported that protein kinase C (PKC) is involved in a negative feedback loop regulating the Kit/SCF-R by direct phosphorylation on serine residues in the receptor. Inhibition of PKC led to increased SCF-induced tyrosine kinase activity and mitogenicity, but PKC was necessary for SCF-induced motility. In this report we have further examined the modulatory role of PKC on SCF-induced signaling. The ligand-activated Kit/SCF-R associated weakly with GRB2 and induced only little tyrosine phosphorylation of phospholipase C-gamma in porcine aortic endothelial cells transfected with Kit/SCF-R. In contrast, the SCF-stimulated Kit/SCF-R associated efficiently with, and induced tyrosine phosphorylation of, the p85 alpha regulatory subunit of phosphatidyl inositide-3'-kinase (PI-3'-kinase). Both receptor association and tyrosine phosphorylation of p85 alpha were increased after inhibition of PKC, while its serine phosphorylation was decreased. Concomitantly, the specific activity of receptor-associated PI-3'-kinase activity was increased. Inhibition of PI-3'-kinase with wortmannin inhibited SCF-induced mitogenicity. SCF-induced phosphorylation of Raf-1 and activation of ERK2 still occurred after PKC inhibition but was not increased. In conclusion, SCF-induced PI-3'-kinase activation paralleled the increased SCF-induced mitogenicity after inhibition of PKC. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1784103
- author
- Blume-Jensen, Peter ; Rönnstrand, Lars LU ; Gout, Ivan ; Waterfield, Michael D. and Heldin, Carl-Henrik
- publishing date
- 1994
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Signal Transducing Androstadienes/pharmacology Animals Aorta/anatomy & histology Endothelium, Colony-Stimulating Factor/genetics/*metabolism Recombinant Proteins/metabolism *Signal Transduction Stem Cell Factor Swine Transfection Type C Phospholipases/metabolism Tyrosine/metabolism, *Adaptor Proteins, Vascular/cytology GRB2 Adaptor Protein Hematopoietic Cell Growth Factors/metabolism Isoenzymes/metabolism Mitogen-Activated Protein Kinase 1 Phosphatidylinositol 3-Kinases Phosphorylation Phosphotransferases (Alcohol Group Acceptor)/metabolism Protein Kinase C/*metabolism Protein-Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Proteins/metabolism Proto-Oncogene Proteins/genetics/*metabolism Proto-Oncogene Proteins c-kit Proto-Oncogene Proteins c-raf Receptor Protein-Tyrosine Kinases/genetics/*metabolism Receptors
- in
- Journal of Biological Chemistry
- volume
- 269
- issue
- 34
- pages
- 21793 - 21802
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- scopus:0027965243
- ISSN
- 1083-351X
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- c93356e0-8094-4688-aa8d-de9c671bd0bb (old id 1784103)
- alternative location
- http://www.jbc.org/content/269/34/21793.short
- date added to LUP
- 2016-04-04 08:41:37
- date last changed
- 2021-01-03 05:03:52
@article{c93356e0-8094-4688-aa8d-de9c671bd0bb, abstract = {{The Kit/stem cell factor receptor (Kit/SCF-R) is a transmembrane tyrosine kinase receptor of importance for the normal development of hemopoietic cells, melanoblasts, and germ cells. We recently reported that protein kinase C (PKC) is involved in a negative feedback loop regulating the Kit/SCF-R by direct phosphorylation on serine residues in the receptor. Inhibition of PKC led to increased SCF-induced tyrosine kinase activity and mitogenicity, but PKC was necessary for SCF-induced motility. In this report we have further examined the modulatory role of PKC on SCF-induced signaling. The ligand-activated Kit/SCF-R associated weakly with GRB2 and induced only little tyrosine phosphorylation of phospholipase C-gamma in porcine aortic endothelial cells transfected with Kit/SCF-R. In contrast, the SCF-stimulated Kit/SCF-R associated efficiently with, and induced tyrosine phosphorylation of, the p85 alpha regulatory subunit of phosphatidyl inositide-3'-kinase (PI-3'-kinase). Both receptor association and tyrosine phosphorylation of p85 alpha were increased after inhibition of PKC, while its serine phosphorylation was decreased. Concomitantly, the specific activity of receptor-associated PI-3'-kinase activity was increased. Inhibition of PI-3'-kinase with wortmannin inhibited SCF-induced mitogenicity. SCF-induced phosphorylation of Raf-1 and activation of ERK2 still occurred after PKC inhibition but was not increased. In conclusion, SCF-induced PI-3'-kinase activation paralleled the increased SCF-induced mitogenicity after inhibition of PKC.}}, author = {{Blume-Jensen, Peter and Rönnstrand, Lars and Gout, Ivan and Waterfield, Michael D. and Heldin, Carl-Henrik}}, issn = {{1083-351X}}, keywords = {{Signal Transducing Androstadienes/pharmacology Animals Aorta/anatomy & histology Endothelium; Colony-Stimulating Factor/genetics/*metabolism Recombinant Proteins/metabolism *Signal Transduction Stem Cell Factor Swine Transfection Type C Phospholipases/metabolism Tyrosine/metabolism; *Adaptor Proteins; Vascular/cytology GRB2 Adaptor Protein Hematopoietic Cell Growth Factors/metabolism Isoenzymes/metabolism Mitogen-Activated Protein Kinase 1 Phosphatidylinositol 3-Kinases Phosphorylation Phosphotransferases (Alcohol Group Acceptor)/metabolism Protein Kinase C/*metabolism Protein-Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Proteins/metabolism Proto-Oncogene Proteins/genetics/*metabolism Proto-Oncogene Proteins c-kit Proto-Oncogene Proteins c-raf Receptor Protein-Tyrosine Kinases/genetics/*metabolism Receptors}}, language = {{eng}}, number = {{34}}, pages = {{21793--21802}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Modulation of Kit/stem cell factor receptor-induced signaling by protein kinase C}}, url = {{http://www.jbc.org/content/269/34/21793.short}}, volume = {{269}}, year = {{1994}}, }