{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":54,"searchCount":0},"additional":{"omics_type":["Unknown"],"volume":["11(3)"],"submitter":["Grossmann A"],"pubmed_abstract":["Post-translational protein modifications, such as tyrosine phosphorylation, regulate protein-protein interactions (PPIs) critical for signal processing and cellular phenotypes. We extended an established yeast two-hybrid system employing human protein kinases for the analyses of phospho-tyrosine (pY)-dependent PPIs in a direct experimental, large-scale approach. We identified 292 mostly novel pY-dependent PPIs which showed high specificity with respect to kinases and interacting proteins and validated a large fraction in co-immunoprecipitation experiments from mammalian cells. About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes. Network analysis revealed that pY-mediated recognition events are tied to a highly connected protein module dedicated to signaling and cell growth pathways related to cancer. Using binding assays, protein complementation and phenotypic readouts to characterize the pY-dependent interactions of TSPAN2 (tetraspanin 2) and GRB2 or PIK3R3 (p55γ), we exemplarily provide evidence that the two pY-dependent PPIs dictate cellular cancer phenotypes."],"journal":["Molecular systems biology"],"pagination":["794"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4380928"],"repository":["biostudies-literature"],"pubmed_title":["Phospho-tyrosine dependent protein-protein interaction network."],"pmcid":["PMC4380928"],"pubmed_authors":["Benlasfer N","Grossmann A","Wachsmuth F","Stelzl U","Hegele A","Birth P","Apelt L"],"view_count":["54"],"additional_accession":[]},"is_claimable":false,"name":"Phospho-tyrosine dependent protein-protein interaction network.","description":"Post-translational protein modifications, such as tyrosine phosphorylation, regulate protein-protein interactions (PPIs) critical for signal processing and cellular phenotypes. We extended an established yeast two-hybrid system employing human protein kinases for the analyses of phospho-tyrosine (pY)-dependent PPIs in a direct experimental, large-scale approach. We identified 292 mostly novel pY-dependent PPIs which showed high specificity with respect to kinases and interacting proteins and validated a large fraction in co-immunoprecipitation experiments from mammalian cells. About one-sixth of the interactions are mediated by known linear sequence binding motifs while the majority of pY-PPIs are mediated by other linear epitopes or governed by alternative recognition modes. Network analysis revealed that pY-mediated recognition events are tied to a highly connected protein module dedicated to signaling and cell growth pathways related to cancer. Using binding assays, protein complementation and phenotypic readouts to characterize the pY-dependent interactions of TSPAN2 (tetraspanin 2) and GRB2 or PIK3R3 (p55γ), we exemplarily provide evidence that the two pY-dependent PPIs dictate cellular cancer phenotypes.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Mar","modification":"2024-11-08T09:15:03.695Z","creation":"2019-03-27T01:49:09Z"},"accession":"S-EPMC4380928","cross_references":{"pubmed":["25814554"],"doi":["10.15252/msb.20145968"]}}