Members of the src family of nonreceptor tyrosine kinases share a common mechanism for membrane binding.
The src family of nonreceptor protein tyrosine kinases share extensive sequence homology, except for 80 NH2-terminal amino acids, thought to comprise a "unique" domain. This region is presumed to mediate interactions specific to each kinase. Recently, we identified three NH2-terminal lysine residues, crucial for pp60v-src membrane association. Surprisingly, these lysines are conserved among several src family members. Since their mechanism of membrane association is unknown, it was of interest to determine whether other tyrosine kinases also utilize their NH2-terminal domain. Here, we demonstrate that pp60v-src, p62c-yes, and p59fyn polypeptides compete with each other for membrane binding, whereas p56lck, which lacks the NH2-terminal lysine motif, has no effect. Moreover, myristylated peptides corresponding to the NH2 termini of src, yes, lyn, and fyn inhibit membrane association of pp60c-src, p62c-yes, and p59fyn. Our results suggest that src family members share a common mechanism for membrane binding, and they provide a molecular explanation for the ability of other src family members to complement pp60c-src function.
Department of Cell Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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D000478:Alkylation; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism*; D016384:Consensus Sequence; D016391:Genes, src; D008239:Lysine; D051379:Mice; D005810:Multigene Family; D019814:Myristic Acid; D009227:Myristic Acids; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D009227:Myristic Acids; D010446:Peptide Fragments; D019814:Myristic Acid; D011505:Protein-Tyrosine Kinases; D008239:Lysine