Open AccessPhospho‐tyrosine dependent protein–protein interaction network
Author(s) -
Grossmann Arndt,
Benlasfer Nouhad,
Birth Petra,
Hegele Anna,
Wachsmuth Franziska,
Apelt Luise,
Stelzl Ulrich
Publication year - 2015
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20145968
Subject(s) - biology , immunoprecipitation , protein–protein interaction , phosphorylation , phenotype , complementation , microbiology and biotechnology , protein fragment complementation assay , plasma protein binding , tyrosine phosphorylation , tyrosine , signal transduction , tyrosine kinase , receptor tyrosine kinase , computational biology , genetics , biochemistry , gene
Post‐translational protein modifications, such as tyrosine phosphorylation, regulate protein–protein interactions ( PPI s) 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 PPI s in a direct experimental, large‐scale approach. We identified 292 mostly novel pY ‐dependent PPI s 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 ‐ PPI s 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 TSPAN 2 (tetraspanin 2) and GRB 2 or PIK 3R3 (p55γ), we exemplarily provide evidence that the two pY ‐dependent PPI s dictate cellular cancer phenotypes.