The src protein contains multiple domains for specific attachment to membranes.
The proteins encoded by the oncogene v-src and its cellular counterpart c-src (designated generically here as pp60src) are tightly associated with both plasma membranes and intracellular membranes. This association is due in part to the amino-terminal myristylation of pp60src, but several lines of evidence suggest that amino-terminal portions of the protein itself are also involved. We now report that pp60src contains at least three domains which, in conjunction with myristylation, are capable of mediating attachment to membranes and determining subcellular localization. We identified these domains by fusing various portions of pp60src to pyruvate kinase, which is normally a cytoplasmic protein. Amino acids 1 to 14 of pp60src 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 pp60src contains independent domains that target the protein to distinctive subcellular locations and thus may facilitate diverse biological functions of the protein.
G.W. Hooper Research Foundation, University of California Medical Center, San Francisco 94143.
J M
JM
Kaplan
H E
HE
Varmus
J M
JM
Bishop
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D005455:Fluorescent Antibody Technique; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000648:ultrastructure; D016392:Proto-Oncogene Proteins pp60(c-src); D011770:Pyruvate Kinase / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D008565:Membrane Proteins; D009227:Myristic Acids; D011518:Proto-Oncogene Proteins; D019814:Myristic Acid; D011770:Pyruvate Kinase; D015688:Oncogene Protein pp60(v-src); D016392:Proto-Oncogene Proteins pp60(c-src)