Transduction of circular membrane ruffling by the platelet-derived growth factor beta-receptor is dependent on its kinase insert.
The platelet-derived growth factor (PDGF) alpha- and beta-receptors both mediate a mitogenic response, but only the beta-receptor mediates circular actin reorganization and chemotaxis. The tyrosine kinase domains of the receptors contain noncatalytic inserts of about 100 residues. In order to determine the role of these domains in the differential signaling of the two receptors, we constructed chimeric PDGF receptors and expressed the constructs in porcine aortic endothelial cells. The chimeric receptors were similar to the wild-type receptors in their ability to induce mitogenicity in response to ligand. Examination of receptor-associated substrates by in vitro kinase assays revealed that phosphoproteins of 72 and 110 kilodaltons were associated with the kinase insert of the alpha-receptor, whereas a phosphoprotein of 130 kilodaltons was associated with the kinase insert of the beta-receptor. Actin reorganization in the form of circular membrane ruffling was seen after ligand stimulation of the beta-receptor and the alpha-receptor containing the beta-receptor kinase insert but not after stimulation of the alpha-receptor or the beta-receptor containing the alpha-receptor kinase insert. These data indicate that the PDGF beta-receptor kinase insert has an essential function in the signal transduction pathway leading to circular membrane ruffling.
Arvidsson
A K
AK
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Heldin
C H
CH
Claesson-Welsh
L
L
D000199:Actins / Q000648:ultrastructure; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D008934:Mitogens / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology*
D000199:Actins; D008934:Mitogens; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor