Processing of p60v-src to its myristylated membrane-bound form.
p60src of wild-type Rous sarcoma virus is myristylated at its N-terminal glycine residue. We have shown previously that this myristylation is necessary for p60src membrane association and for cell transformation by using src mutants with alterations within the N-terminal 30 kilodaltons of p60src. In this study we analyzed the process of p60src myristylation in wild type- and mutant-infected cells. All myristylated src proteins examined lack the initiator methionine, but two mutant src proteins lacking the initiator methionine are not myristylated, indicating that removal of the initiator methionine and myristylation are not obligatorily coupled. Analysis of the kinetics of myristylation and the association of p60src with cellular proteins p50 and p90 indicated that myristylation occurs before p60src becomes membrane associated and that transient association with p50 and p90 occurs regardless of myristylation. Myristylation is required for stable association of p60src with the plasma membrane but is not sufficient for membrane association. A mutant with an src deletion of amino acids 169 through 264 has an src protein that is myristylated but not membrane bound, remaining stably associated with p50 and p90. This mutant is transformation defective. Several N-terminal deletion mutants possessing tyrosine kinase activity have myristylated and membrane-bound src proteins but are not fully active in cell transformation, suggesting that additional N-terminal functional domains exist.
D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000378:metabolism; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D002472:Cell Transformation, Viral; D002642:Chick Embryo; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D009154:Mutation; D009226:Myristates / Q000378:metabolism*; D009227:Myristic Acids / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src); D011499:Protein Processing, Post-Translational; D012191:Retroviridae Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D008565:Membrane Proteins; D009226:Myristates; D009227:Myristic Acids; D012191:Retroviridae Proteins; D008715:Methionine; D015688:Oncogene Protein pp60(v-src)