title: Analysis of EphA4 receptor tyrosine kinase substrate specificity using peptide-based arrays.
abstract: Eph receptor tyrosine kinases regulate many important biological processes. In the present study, we explored the substrate specificity of the EphA4 receptor tyrosine kinase using peptide arrays. We define a consensus substrate motif for EphA4 and go on to identify and test a number of potential EphA4 substrates and map their putative site(s) of phosphorylation. Cotransfection studies validate two of the predicted substrates: Nck2 and Dok1. Our findings identify several potential EphA4 substrates and demonstrate the general utility of using peptide arrays to rapidly identify and map protein kinase phosphorylation sites.
authors.affiliation: Program in Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Warner
authors.forename: Leanne E
authors.initials: LE
authors.lastname: Wybenga-Groot
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D040081:Protein Array Analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489561:Dok1 protein, mouse; C117758:Nck2 protein, mouse; D015513:Oncogene Proteins; D010455:Peptides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014443:Tyrosine; D036122:Receptor, EphA4