Increased Kit/SCF receptor induced mitogenicity but abolished cell motility after inhibition of protein kinase C
Blume-Jensen, Peter ; Siegbahn, Agneta ; Stabel, Silvia ; Heldin, Carl-Henrik and Rönnstrand, Lars LU
(1993)
In EMBO Journal
12(11).
p.4199-4209
- Abstract
- The product of the c-kit proto-oncogene, denoted Kit/SCF-R, encodes a tyrosine kinase receptor for stem cell factor (SCF). Kit/SCF-R induces proliferation, differentiation or migration of cells within the hematopoietic, gametogenic and melanogenic lineages at different developmental stages. We report here that protein kinase C (PKC) mediates phosphorylation of Kit/SCF-R on serine residues in response to SCF or PMA in intact cells. The phosphorylation inhibits SCF-induced tyrosine autophosphorylation of Kit/SCF-R. In vitro studies showed that PKC phosphorylated the Kit/SCF-R directly on serine residues and inhibited autophosphorylation of Kit/SCF-R, as well as its kinase activity towards an exogenous substrate. The PKC-induced... (More)
- The product of the c-kit proto-oncogene, denoted Kit/SCF-R, encodes a tyrosine kinase receptor for stem cell factor (SCF). Kit/SCF-R induces proliferation, differentiation or migration of cells within the hematopoietic, gametogenic and melanogenic lineages at different developmental stages. We report here that protein kinase C (PKC) mediates phosphorylation of Kit/SCF-R on serine residues in response to SCF or PMA in intact cells. The phosphorylation inhibits SCF-induced tyrosine autophosphorylation of Kit/SCF-R. In vitro studies showed that PKC phosphorylated the Kit/SCF-R directly on serine residues and inhibited autophosphorylation of Kit/SCF-R, as well as its kinase activity towards an exogenous substrate. The PKC-induced phosphorylation did not affect Kit/SCF-R ligand binding affinity. Inhibition of PKC led to increased SCF-induced tyrosine autophosphorylation, as well as increased SCF-induced mitogenicity. In contrast, PKC was necessary for SCF-induced motility responses, including actin reorganization and chemotaxis. Our data suggest that PKC is involved in a negative feedback loop which regulates the Kit/SCF-R and that the activity of PKC determines whether the effect of SCF will be preferentially mitogenic or motogenic. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1784137
- author
- Blume-Jensen, Peter
; Siegbahn, Agneta
; Stabel, Silvia
; Heldin, Carl-Henrik
and Rönnstrand, Lars
LU
- publishing date
- 1993
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Vascular/drug effects/enzymology/*growth & developmentHematopoietic Cell Growth Factors/pharmacologyHumans*NaphthalenesPhosphorylationPolycyclic Compounds/pharmacologyProtein Kinase C/antagonists & inhibitors/*metabolismProto-Oncogene Proteins/*metabolismProto-Oncogene Proteins c-kitReceptor Protein-Tyrosine Kinases/*metabolismReceptors, CulturedChemotaxisEndothelium, AnimalsAorta/cytologyCell Division/drug effects*Cell Movement/drug effectsCells, Colony-Stimulating Factor/*metabolismSerine/metabolismStem Cell FactorSwine
- in
- EMBO Journal
- volume
- 12
- issue
- 11
- pages
- 4199 - 4209
- publisher
- Oxford University Press
- external identifiers
-
- scopus:0027508336
- ISSN
- 1460-2075
- 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
- 1585a467-b048-4ee9-acc2-ae5d0822cc87 (old id 1784137)
- alternative location
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC413714/
- date added to LUP
- 2016-04-04 09:23:29
- date last changed
- 2021-03-14 05:44:22
@article{1585a467-b048-4ee9-acc2-ae5d0822cc87,
abstract = {{The product of the c-kit proto-oncogene, denoted Kit/SCF-R, encodes a tyrosine kinase receptor for stem cell factor (SCF). Kit/SCF-R induces proliferation, differentiation or migration of cells within the hematopoietic, gametogenic and melanogenic lineages at different developmental stages. We report here that protein kinase C (PKC) mediates phosphorylation of Kit/SCF-R on serine residues in response to SCF or PMA in intact cells. The phosphorylation inhibits SCF-induced tyrosine autophosphorylation of Kit/SCF-R. In vitro studies showed that PKC phosphorylated the Kit/SCF-R directly on serine residues and inhibited autophosphorylation of Kit/SCF-R, as well as its kinase activity towards an exogenous substrate. The PKC-induced phosphorylation did not affect Kit/SCF-R ligand binding affinity. Inhibition of PKC led to increased SCF-induced tyrosine autophosphorylation, as well as increased SCF-induced mitogenicity. In contrast, PKC was necessary for SCF-induced motility responses, including actin reorganization and chemotaxis. Our data suggest that PKC is involved in a negative feedback loop which regulates the Kit/SCF-R and that the activity of PKC determines whether the effect of SCF will be preferentially mitogenic or motogenic.}},
author = {{Blume-Jensen, Peter and Siegbahn, Agneta and Stabel, Silvia and Heldin, Carl-Henrik and Rönnstrand, Lars}},
issn = {{1460-2075}},
keywords = {{Vascular/drug effects/enzymology/*growth & developmentHematopoietic Cell Growth Factors/pharmacologyHumans*NaphthalenesPhosphorylationPolycyclic Compounds/pharmacologyProtein Kinase C/antagonists & inhibitors/*metabolismProto-Oncogene Proteins/*metabolismProto-Oncogene Proteins c-kitReceptor Protein-Tyrosine Kinases/*metabolismReceptors; CulturedChemotaxisEndothelium; AnimalsAorta/cytologyCell Division/drug effects*Cell Movement/drug effectsCells; Colony-Stimulating Factor/*metabolismSerine/metabolismStem Cell FactorSwine}},
language = {{eng}},
number = {{11}},
pages = {{4199--4209}},
publisher = {{Oxford University Press}},
series = {{EMBO Journal}},
title = {{Increased Kit/SCF receptor induced mitogenicity but abolished cell motility after inhibition of protein kinase C}},
url = {{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC413714/}},
volume = {{12}},
year = {{1993}},
}