An N-terminal peptide from p60^src can direct myristylation and plasma membrane localization when fused to heterologous proteins

Abstract

The src gene product, p60^src, of Rous sarcoma virus (RSV) is a tyrosine-specific protein kinase which is associated with the plasma membrane of infected cells (for review, see ref. 1). Myristic acid is bound in an amide linkage to glycine 2 of p60^src (refs 2–6). Of the N-terminal 30 kilodaltons of p60^src only amino acids 1–14 are required for myristylation, and myristylation of p60^src may be required for its membrane association, and for cell transformation^4,7. To test the hypothesis that the first 14 amino acids of p60^src contain a recognition sequence for myristylation, we have fused the DNA sequence coding for these amino acids to either the fps gene of the F36 derivative of Fujinami sarcoma virus (FSV)^8,9, or to the chimpanzee α-globin gene¹⁰. We report here that although the fusion proteins were myristylated, the parental proteins were not, and unlike the non-myristylated F36 p91^fps which was not bound to the plasma membrane, the myristylated fusion protein was bound, like p60^src. We conclude that the first 14 amino acids of p60^src contain a sequence which is sufficient for myristylation, and which may direct proteins to the plasma membrane.