SPECIFIC INTERACTION BETWEEN THE BOVINE PAPILLOMAVIRUS E5 TRANSFORMING PROTEIN AND THE BETA-RECEPTOR FOR PLATELET-DERIVED GROWTH-FACTOR IN STABLY TRANSFORMED AND ACUTELY TRANSFECTED CELLS

The E5 protein of bovine papillomavirus is a 44-amino-acid membrane pr otein which induces morphologic and tumorigenic transformation of fibr oblasts. We previously showed that the E5 protein activates and forms a complex with the endogenous beta receptor for platelet-derived growt h factor (PDGF) in transformed rodent fibroblasts and that the PDGF be ta receptor can mediate tumorigenic transformation by the E5 protein i n a heterologous cell system. Other workers have identified the recept or for epidermal growth factor (EGF) as a potential target of the E5 p rotein in NIH 3T3 cells. Here, we investigate the specificity of the i nteraction of the E5 protein with various growth factor receptors, wit h particular emphasis on the PDGF beta receptor and the EGF receptor. Under conditions where bath the PDGF beta receptor and the EGF recepto r are stably expressed in ES-transformed mouse and bovine fibroblasts and in E5-transformed epithelial cells, the E5 protein specifically fo rms a complex with and activates the PDGF receptor and not the EGF rec eptor. Under conditions of transient overexpression in COS cells, the E5 protein has the potential to associate with several growth factor r eceptors, including the EGF receptor. However, upon coexpression of PD GF beta receptors and EGF receptors in COS cells, the E5 protein prefe rentially forms a complex with the PDGF receptor. Therefore, we conclu de that the PDGF beta receptor is the primary target for the E5 protei n in a variety of cell types, including bovine fibroblasts.