title: Two PDGF-B chain residues, arginine 27 and isoleucine 30, mediate receptor binding and activation.
abstract: PDGF may be involved in the pathogenesis of a variety of disorders including atherosclerosis and certain types of cancer. There is currently little understanding of the molecular structure of PDGF and of the critical amino acid residues involved in receptor binding and cell activation. Two such PDGF-B chain residues, arginine 27 and isoleucine 30, have been identified by a site-directed mutagenesis programme. Substitutions in these positions can lead to PDGF mutants defective in both receptor affinity and cell activation as judged by displacement of [125I]PDGF-BB, mitogenic assay and inositol lipid turnover. Circular dichroism and fluorescence spectroscopy show that such mutations do not disrupt the structure of PDGF.
authors.affiliation: British Bio-technology Ltd, Oxford, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Clements
authors.forename: L J
authors.initials: LJ
authors.lastname: Bawden
authors.forename: R E
authors.initials: RE
authors.lastname: Bloxidge
authors.forename: G
authors.initials: G
authors.lastname: Catlin
authors.forename: A L
authors.initials: AL
authors.lastname: Cook
authors.forename: S
authors.initials: S
authors.lastname: Craig
authors.forename: A H
authors.initials: AH
authors.lastname: Drummond
authors.forename: R M
authors.initials: RM
authors.lastname: Edwards
authors.forename: A
authors.initials: A
authors.lastname: Fallon
authors.forename: D R
authors.initials: DR
authors.lastname: Green
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D005454:Fluorescence Polarization; D007294:Inositol / Q000378:metabolism; D007532:Isoleucine / Q000378:metabolism*; D051379:Mice; D008934:Mitogens; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor
chemical_list: D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D007532:Isoleucine; D007294:Inositol; D001120:Arginine; D017479:Receptors, Platelet-Derived Growth Factor