title: Amino-terminal palmitate or polybasic domain can provide required second signal to myristate for membrane binding of p56lck.
abstract: Recent work has shown that several members of the src family of protein tyrosine kinases (PTKs) are modified by palmitoylation, including p56lck and p59fyn but not p60src. Mapping of the sites of palmitoylation in p56lck identified cys3 as the major site and cys5 as a minor site of palmitoylation. A non-palmitoylated p56lck(cys3,5-->ser) mutant was localized exclusively in the cytoplasm despite the presence of amino-terminal myristoylation, thus indicating that palmitoylation of p56lck was necessary for membrane binding. The addition of a domain of six lysine residues to a non-palmitoylated p56lck mutant was sufficient to re-establish membrane binding but not to target the non-palmitoylated p56lck to caveolae. These results establish that two signals, myristoylation plus either palmitoylation or a polybasic domain, are necessary for membrane binding of src family PTKs.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110-1093.
authors.forename: J
authors.initials: J
authors.lastname: Kwong
authors.forename: D M
authors.initials: DM
authors.lastname: Lublin
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003545:Cysteine; D006367:HeLa Cells; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism*; D010957:Plasmids; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D014162:Transfection
chemical_list: D009227:Myristic Acids; D011994:Recombinant Proteins; D019814:Myristic Acid; D012694:Serine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D003545:Cysteine