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Activation of the human c-kit product by ligand-induced dimerization mediates circular actin reorganization and chemotaxis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
AMGEN Inc., AMGEN Center, Thousand Oaks, CA 91320, USA.
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1991 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 10, no 13, 4121-4128 p.Article in journal (Refereed) Published
Abstract [en]

The proto-oncogene c-kit is allelic with the murine white spotting (W) locus and encodes a transmembrane protein tyrosine kinase that is structurally related to the receptors for platelet-derived growth factor (PDGF) and colony-stimulating factor-1 (CSF-1). Recently the ligand for the c-kit product, stem cell factor (SCF), was identified in both transmembrane and soluble forms. In order to examine the mechanism for receptor activation by SCF and biological properties of the activated c-kit product, we transfected the wild-type human c-kit cDNA into porcine aortic endothelial cells. We found that the receptor was down-regulated and transmitted a mitogenic signal in response to stimulation with soluble SCF. We also demonstrate that SCF induces dimerization of the c-kit product in intact cells, and that dimerization of the receptor is correlated with activation of its kinase. Activation of the c-kit product by SCF was found to induce circular actin reorganization indistinguishable from that mediated by the PDGF beta-receptor in response to PDGF-BB. Furthermore, soluble SCF was a potent chemotactic agent for cells expressing the c-kit product, a property which might be of importance during embryonic development.

Place, publisher, year, edition, pages
1991. Vol. 10, no 13, 4121-4128 p.
Keyword [en]
Actins/*metabolism, Animals, Blotting; Western, Cells; Cultured, Chemotaxis, Cross-Linking Reagents, Cytoskeleton/metabolism, Electrophoresis; Polyacrylamide Gel, Endothelium; Vascular/cytology/metabolism, Hematopoietic Cell Growth Factors/*pharmacology, Humans, Ligands, Phosphorylation, Precipitin Tests, Protein-Tyrosine Kinase/*metabolism, Proto-Oncogene Protein c-kit, Proto-Oncogene Proteins/biosynthesis/*metabolism, Recombinant Proteins/pharmacology, Research Support; Non-U.S. Gov't, Stem Cell Factor, Swine, Thymidine/metabolism
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-73230PubMedID: 1721869OAI: oai:DiVA.org:uu-73230DiVA: diva2:101141
Available from: 2005-06-01 Created: 2005-06-01 Last updated: 2017-12-14Bibliographically approved

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Claesson-Welsh, LenaSiegbahn, AgnetaWestermark, BengtHeldin, Carl-Henrik

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