MUTATIONAL ANALYSIS OF THE BETA-TYPE PLATELET-DERIVED GROWTH-FACTOR RECEPTOR DEFINES THE SITE OF INTERACTION WITH THE BOVINE PAPILLOMAVIRUSTYPE-1 E5 TRANSFORMING PROTEIN

The E5 polypeptide of bovine papillomavirus type 1 is a small membrane -bound protein which induces the transformation of immortalized fibrob lasts, apparently via the formation of a ternary complex with the plat elet-derived growth factor receptor (PDGFR) and the 16-kDa V-ATPase pr otein. This interaction seems to be mediated, at least in part, by the ir respective transmembrane domains. E5 also cooperates with transfect ed beta PDGFR to induce interleukin-3 (IL-3)-independent growth of a m ouse myeloid precursor cell line (32D) which normally lacks expression of most known tyrosine kinase growth factor receptors. Cell prolifera tion induced by beta PDGFR and E5 is also highly specific, since the h ighly conserved alpha PDGFR and other related receptors did not physic ally or functionally interact with E5 in these cells. In the current s tudy, analysis of chimeric alpha and beta PDGFRs confirmed that a shor t region encompassing the beta PDGFR transmembrane domain was sufficie nt for complex formation with E5, receptor autophosphorylation, and su stained proliferation of 32D cells in the absence of IL-3. Furthermore , a deletion mutant lacking the entire extracellular domain efficientl y bound E5 and induced IL-3-independent growth. These data provide dir ect evidence that the interaction between E5 and the beta PDGFR involv es amino acids 531 to 556 of the receptor transmembrane region and tha t this specific interaction is critical for activation of the PDGFR si gnalling complex.