B-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein-tyrosine kinase.
Porcine aorta endothelial cells are devoid of receptors for platelet-derived growth factor (PDGF). We have transfected such cells with cDNA for the PDGF B-type receptor, both the wild-type receptor and a mutant form of the receptor (K634A), in which the putative nucleotide-binding lysine of the protein-tyrosine domain has been changed to alanine. Immunoprecipitation studies of metabolically labeled cells showed that both types of receptors were synthesized and processed to the mature form of Mr 190,000. In cells expressing the wild-type receptor, PDGF-BB, the natural ligand for the B-type receptor, induced membrane ruffling and reorganization of actin. Such a response has previously been seen in cells expressing the natural PDGF B-type receptor in response to PDGF-BB. No such effect was induced in nontransfected cells or in cells expressing the K634A mutant receptor. PDGF was also shown to be chemotactic for cells expressing the wild-type receptor, whereas no chemotactic response was elicited in control cells or in cells expressing the K634A mutant receptor. Our study thus provides formal evidence that the PDGF B-type receptor mediates a motility response including actin reorganization and chemotaxis. Furthermore, the results establish a role for the receptor-associated protein-tyrosine kinase in the transduction of the chemotactic signal.
Westermark
B
B
Department of Pathology, University of Uppsala, Sweden.
Siegbahn
A
A
Heldin
C H
CH
Claesson-Welsh
L
L
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002633:Chemotaxis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D004789:Enzyme Activation; D007700:Kinetics; D008024:Ligands; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D013552:Swine; D014162:Transfection
D008024:Ligands; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor