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^1,2. One of the few carcinoma-inducing viruses is the acutely transforming retrovirus MH2 (refs 2,3), which carries the putative oncogene v-mil and the known oncogene v-myc(refs 4–6). Recently, a high degree of homology was discovered between v-mil and v-raf (ref. 7), the transforming gene of the murine retrovirus 3611 murine sarcoma virus (MSV)⁸, whereas homology to v-src is low⁹. Both viruses express their oncogenes as the gag-fusion polyproteins^6,10 p100^gag-mil and p75^gag-raf (of respective relative molecular mass (M_r) 100,000 and 75,000), while the myc oncogene of MH2 is expressed by means of a subgenomic messenger RNA¹¹. We have recently demonstrated that p100^gag-mil is not a nuclear protein⁶. Here we report that purified p100^gag-mil and p75^gag-raf exhibit protein kinase activities in vitro which, in contrast to the src-related p130^gag-fps of Fujinami sarcoma virus (FSV)¹² and all other characterized oncogene-encoded protein kinases, phosphorylate serine and threonine but not tyrosine. Both types of protein kinases phosphorylate lipids in vitro.