Dr Cristinna Gewinner, Requirement for primed residues in the substrate phosphorylation motif of receptor tyrosine and nonreceptor tyrosine kinases
Date: Wed 22 Apr 2015, 15:00 - 16:00
Location: Derek Willoughby Lecture Theatre, John Vane Science Centre, Charterhouse Square
SPEAKER: Dr Cristinna Gewinner Research Department of Cancer Biology, University College London
TITLE: “Requirement for primed residues in the substrate phosphorylation motif of receptor tyrosine and nonreceptor tyrosine kinases”
DATE & LOCATION: Wednesday April 22nd , 2014, 3-4pm, in Derek Willoughby Lecture Theatre, John Vane Science Centre, Charterhouse Square.
Protein-tyrosine kinase inhibitors have been approved for treating a wide range of cancers. A detailed knowledge of protein-Tyr kinase signaling networks is needed to provide a logic for selecting drug combinations that are likely to be effective. However, one aspect of protein kinase biology that remains poorly understood is how kinases achieve specificity for their target substrates. Here, we have adapted a new positional scanning peptide library approach to address the substrate specificity of protein-tyrosine kinases. We examined the substrate sequence preferences of eight different receptor and non-receptor tyrosine kinases. Strikingly, we found that several of the tyrosine kinases, including c-Met, strongly selected for peptides that were ‘primed’ by prior phosphorylation on Tyr or Tyr residues. We also investigated the effect of a few known oncogenic mutations of protein-Tyr kinases on their peptide substrate specificities. Additionally, incorporating position-specific selectivity matrix generated from these studies into Scansite and PhosphoSitePlus programs, provided predictions of substrates for these kinases.