Structural and functional aspects of platelet-derived growth factor and its receptors.
Platelet-derived growth factor (PDGF) is a dimeric molecule that exists as homodimers or heterodimers of related polypeptide chains (A and B). Two types of PDGF receptor have been identified. The PDGF alpha-receptor binds all three isoforms with high affinity whereas the beta-receptor binds only PDGF-BB with high affinity, PDGF-AB with low affinity and does not appear to bind PDGF-AA. The alpha- and beta-receptors are structurally related, each having an intracellular protein tyrosine kinase domain. Ligand-induced functional activation of the receptors appears to involve receptor dimerization. Binding of PDGF to its receptor is followed by internalization and degradation of the ligand-receptor complex. Experiments with mutant receptors have shown that ligand-induced internalization is not absolutely dependent on the kinase activity of the beta-receptor. The v-sis oncogene of simian sarcoma virus (SSV) is a retroviral version of the PDGF B chain gene and SSV-transformation is mediated by an autocrine PDGF-like growth factor. Formal evidence that the expression of the PDGF beta-receptor is sufficient to confer susceptibility to SSV-transformation has been obtained using porcine endothelial cells expressing a recombinant human beta-receptor. PDGF is a chemotactic agent for several cell types. Recent experiments have shown that the PDGF beta-receptor mediates a chemotactic response and that this effect requires an intact protein tyrosine kinase activity.
Westermark
B
B
Department of Pathology, University Hospital, Uppsala, Sweden.
Claesson-Welsh
L
L
Heldin
C H
CH
D000818:Animals; D006801:Humans; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology*; 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
D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor