Specific Attachment to Membranes

The proteins encoded by the oncogene v-src and its cellular counterpart e-src (designated generically here as p w ? are tightly associated with both plasma membranes and intracellular membranes. This association is due in part to the amino-terminal myristylation of ppWm, but several lines of evidence suggest that amino-terminal portions of the protein itself are also involved. We now report that p w " contains at least three domains which, in conjunction with myristylation, are capable of mediating attachment to membranes and determining subceitular localization. We identified these domains by fusing various portions of p@"" to pyruvate kinase, which is normally a cytoplasmic protein. Amino acids 1 to 14 of ppaoVr are sufficient to mediate both myristylation and the attachment of pyruvate kinase to cytoplasmic granules. In contrast, amino acids 38 to 111 mediate association with the plasma membrane and perinuclear membranes, whereas amino acids 204 to 259 mediate association primarily with perinuclear membranes. We conclude that ppMY" contains independent domains that target the protein to distinctive subcellular locations and thus may facilitate diverse biological functions of the protein.