Identification and Structural Analysis of the A Type Receptor for Platelet-derived Growth Factor

Binding analyses using '261-labeled platelet-derived growth factor (PDGF)-AA and PDGF-BB were used to identify a clonal human glioma cell line (U-343 MGa 31L) which expresses the A type but not the B type receptor for PDGF.The glioma cells were devoid of a B type receptor transcript, and immunoprecipitation with an antiserum raised against a B type receptor peptide rendered no signal.Similar analyses using human foreskin fibroblasts, which express both A and B type PDGF receptors, revealed a B type PDGF receptor-specific 5.5-kilobase pair mRNA in a Northern blot experiment, and 160,000 and 180,000 molecular weight components upon immunoprecipitation.A second antiserum, raised against purified porcine PDGF receptor preparations, was reactive with M, 140,000 and 170,000 components in the U-343 MGa 31L cells, as well as in human fibroblasts.In addition, this antiserum precipitated the M, 160,000 and 180,000 components from the fibroblasts.Exposure of cells to PDGF-AA, as well as to PDGF-BB, induced an increased rate of degradation of the M, 170,000 component in the clonal glioma cells and in fibroblasts.The M, 180,000 component in fibroblasts was degraded only when cells were exposed to PDGF-BB.This allowed the identification of the M, 170,000 component as the cell surface expressed form of the A type receptor for PDGF.A structural relatedness between the A and B type PDGF receptors was furthermore indicated by similarities in peptide patterns, after limited proteolytic digestion.Platelet-derived growth factor (PDGF)' is a major mitogen in serum for connective tissue and glial cells (reviewed in Refs. 1 and 2).It is a disulfide-bonded dimer composed of A and B polypeptide chains, which are about 60% similar in their amino acid sequences (3-5).All possible combinations of A and B chains, AA, AB, and BB, have been identified and purified from platelets or transformed cells (6-13).The various isoforms of PDGF differ in their functional effects on