Association of coatomer proteins with the beta-receptor for platelet-derived growth factor.
The nonreceptor tyrosine kinase Src binds to and is activated by the beta-receptor for platelet-derived growth factor (PDGF). The interaction leads to Src phosphorylation of Tyr934 in the kinase domain of the receptor. In the course of the functional characterization of this phosphorylation, we noticed that components of 136 and 97 kDa bound to a peptide from this region of the receptor in a phosphorylation-independent manner. These components have now been purified and identified as alpha- and beta'-coatomer proteins (COPs), respectively. COPs are a family of proteins involved in the regulation of intracellular vesicle transport. In order to explore the functional significance of the interaction between alpha- and beta'-COP and the PDGF receptor, a receptor mutant was made in which the conserved histidine residue 928 was mutated to an alanine residue. The mutant receptor, which was unable to bind alpha- or beta'-COP, showed a normal ligand-induced autophosphorylation. The mutant receptor also behaved like the wildtype receptor with regard to biosynthesis and maturation, and mediated a mitogenic signal. The possible functional importance of the interaction between the PDGF beta-receptor and alpha- and beta'-COP, is discussed.
Hansen
K
K
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Rönnstrand
L
L
Rorsman
C
C
Hellman
U
U
Heldin
C H
CH
D000595:Amino Acid Sequence; D001665:Binding Sites; D002846:Chromatography, Affinity; D020756:Coatomer Protein; D017124:Conserved Sequence; D006367:HeLa Cells; D006639:Histidine; D006801:Humans; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D010766:Phosphorylation; D017354:Point Mutation; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine; D018909:src Homology Domains
D020756:Coatomer Protein; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D006639:Histidine; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor