Structural and functional aspects of the receptors for platelet-derived growth factor

Prog Growth Factor Res. 1989;1(4):253-66. doi: 10.1016/0955-2235(89)90014-8.

Abstract

Platelet-derived growth factor (PDGF) is a 30 kDa dimer of disulfide-bonded A and B chains. Three isoforms of PDGF have been isolated (PDGF-AA, PDGF-AB and PDGF-BB). These bind with different affinities and specificities to two structurally related cell surface receptors, viz. the alpha-receptor and the beta-receptor. The receptors are transmembrane proteins with an intracellular, ligand-stimulatable protein tyrosine kinase domain. Activation of the receptors is intimately associated with receptor dimerization, and available data suggest that PDGF is a divalent ligand such that one molecule of PDGF binds and dimerizes two receptor molecules. Stimulation of PDGF receptors leads to a cascade of cellular events, which have been shown to require an intact receptor tyrosine kinase activity. However, ligand-induced internalization and degradation of the beta-receptor occur essentially independent of the receptor kinase activity. Receptor activation leads to the phosphorylation on tyrosine residues of three enzymes, probably by direct phosphorylation: phospholipase C-gamma, phosphatidylinositol 3' kinase and Raf-1. In certain cells, PDGF beta-receptor expression is inducible such that cells in normal tissue in vivo do not express receptors; only in inflammatory lesions or when cells are explanted in vitro, are receptors being expressed. Transformation by the v-sis oncogene is mediated by an autocrine PDGF-like growth factor. Although both the alpha- and beta-receptors are structurally related to the v-fms and v-kit oncogenes, it is not known if the PDGF receptors have a transforming potential. In conclusion, the finding of three isoforms of PDGF that interact with two structurally related receptors implies a finely tuned regulatory network, the role of which in cell growth and transformation remains to be clarified.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Transformation, Neoplastic
  • Humans
  • Molecular Sequence Data
  • Platelet-Derived Growth Factor*
  • Protein Conformation
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism*
  • Receptors, Platelet-Derived Growth Factor

Substances

  • Platelet-Derived Growth Factor
  • Receptors, Cell Surface
  • Receptors, Platelet-Derived Growth Factor