Serine- and threonine-specific protein kinase activities of purified gag–mil and gag–raf proteins

Abstract

Retroviruses carry cell-derived oncogenes (v-onc) that have the potential to transform cells in culture and induce tumours in vivo. One of the few carcinoma-inducing viruses is the acutely transforming retrovirus MH2, which carries the putative oncogene v-mil and the known oncogene v-myc. Recently, a high degree of homology was discovered between v-mil and v-raf, the transforming gene of the murine retrovirus 3611 murine sarcoma virus (MSV), whereas homology to v-src is low. Both viruses express their oncogenes as the gag-fusion polyproteins p100gag-mil and p75gag-raf (of respective relative molecular mass (Mr) 100,000 and 75,000), while the myc oncogene of MH2 is expressed by means of a subgenomic messenger RNA. We have recently demonstrated that p100gag-mil is not a nuclear protein. Here we report that purified p100gag-mil and p75gag-raf exhibit protein kinase activities in vitro which, in contrast to the src-related p130gag-fps of Fujinami sarcoma virus (FSV) and all other characterized oncogene-encoded protein kinases, phosphorylate serine and threonine but not tyrosine. Both types of protein kinases phosphorylate lipids in vitro.