Phospho-tyrosine dependent protein-protein interaction network

Grossmann, Arndt; Benlasfer, Nouhad; Birth, Petra; Hegele, Anna K.; Wachsmuth, Franziska; Apelt, Luise; Stelzl, Ulrich

doi:10.15252/msb.20145968

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Phospho-tyrosine dependent protein-protein interaction network

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Grossmann, Arndt
Molecular Interaction Networks (Ulrich Stelzl), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Benlasfer, Nouhad
Molecular Interaction Networks (Ulrich Stelzl), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Birth, Petra
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Hegele, Anna K.
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

Wachsmuth, Franziska
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Apelt, Luise
Molecular Interaction Networks (Ulrich Stelzl), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Stelzl, Ulrich
Molecular Interaction Networks (Ulrich Stelzl), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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http://www.ncbi.nlm.nih.gov/pubmed/25814554
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Citation

Grossmann, A., Benlasfer, N., Birth, P., Hegele, A. K., Wachsmuth, F., Apelt, L., et al. (2015). Phospho-tyrosine dependent protein-protein interaction network. Molecular Systems Biology, 11(3): 0794. doi:10.15252/msb.20145968.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002A-5FDA-3

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 (p55gamma), we exemplarily provide evidence that the two pY-dependent PPIs dictate cellular cancer phenotypes.