p60src, the protein responsible for the oncogenicity of Rous sarcoma virus, is a tyrosine-specific protein kinase. The kinase activity of p60src is essential but is not the only requirement for cellular transformation. A myricstic acid group is covalently attached to the amino terminal glycine residue of p60src. A mutant of p60src in which this amino terminal glycine is replaced with an alanine is not myristylated. The kinase activity of this mutant is unaltered, but the mutant p60src protein does not bind to cellular membranes, and does not transform cells. The myristic acid itself, or the binding to membranes which it induces is thus required for cellular transformation by p60src. We will study the function of the myristic acid for p60src in 4 ways: 1) by measuring directly the membrane-binding of myristylated and non-myristylated peptide analogs of the amino terminus of p60src; 2) by developing an in vitro method of myristylation so that the lipid and substrate specificities of the myristyl transferase may be studied; 3) by determining if nascent polypeptide chains contain myristic acid to learn if proteins become myristylated during synthesis and where the myristyl transferase in located in the cell; 4) by myristylating p60src during in vitro translation of viral RNA to determine if protein synthesis is a requirement for myristylation.
