We propose to analyze the molecular biology of the platelet-derived growth factor (PDGF) receptor. PDGF is the major growth-promoting agent in human blood and interacts with PDGF-specific receptors to induce the growth of connective tissue cells. The PDGF receptor is especially important in this process because it appears to orchestrate the initial events in growth response to PDGF. Furthermore, recent observations suggesting that a protein encoded by an oncogene (PDGF/sis) can induce through the PDGF receptor the expression of another oncogene (c-myc) implies a possible role for the PDGF receptor in certain types of malignant growth. We plan to carry out final purification and protein sequence analysis on the mouse and human PDGF receptor proteins. Synthetic oligonucleotides based on reverse transaction of the amino acid sequence of the PDGF receptor protein, followed by standard DNA walking techniques, will be used to isolate cDNA clones encoding the complete PDGF receptor transcript. The PDGF receptor cDNA clones will be used to isolate and characterize the PDGF receptor gene from cosmid libraries. We plan to sequence the coding and presumed regulatory regions of the PDGF receptor gene. In addition, we plan to examine the role of PDGF and of the PDGR receptor in transformation. We will use DNA-mediated gene transfer to determine if the PDGF receptor gene is capable of acting as a transforming and/or sufficient to make nonresponsive cells responsive to PDGF. We plan to examine a large and diverse panel of nontransformed and transformed derivative cell lines for PDGF and PDGF receptor. (J)
| Tempst, P; Woo, D D; Teplow, D B et al. (1986) Microscale structure analysis of a high-molecular-weight, hydrophobic membrane glycoprotein fraction with platelet-derived growth factor-dependent kinase activity. J Chromatogr 359:403-12 |
