Activation of the human c-kit product by ligand-induced dimerization mediates circular actin reorganization and chemotaxis

• 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.

Nyckelord

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

MEDICINE

MEDICIN

Publikations- och innehållstyp

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