title: Lysine residues form an integral component of a novel NH2-terminal membrane targeting motif for myristylated pp60v-src.
abstract: Association of pp60v-src with the plasma membrane is fundamental to generation of the transformed phenotype. Although myristylation of pp60v-src is required for interaction with a membrane-bound receptor, the importance of NH2-terminal amino acids in receptor binding has not yet been uncoupled from their role in signaling myristylation. Using chimeric src proteins, peptides identical or related to the NH2 terminus of src, and site-directed mutagenesis, we demonstrate that NH2-terminal lysines in conjunction with myristate are essential for membrane localization. Subsequent to NH2-terminal interaction with the "src receptor," internal regions of the src protein also participate in membrane binding. This novel NH2-terminal motif and internal contact mechanism may direct other members of the src family of tyrosine kinases to their membrane receptors.
authors.affiliation: Department of Cell Biology and Genetics, Memorial Sloan-Kettering Cancer, Center, New York 10021.
authors.forename: L
authors.initials: L
authors.lastname: Silverman
authors.forename: M D
authors.initials: MD
authors.lastname: Resh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003411:Arvicolinae; D001692:Biological Transport; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D008239:Lysine; D008969:Molecular Sequence Data; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D009227:Myristic Acids; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D019814:Myristic Acid; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src); D008239:Lysine