The dynamics of the protein-protein interaction network and how it responds to biological perturbations remain difficult to assay by most traditional techniques. A novel kinase-dependent yeast two-hybrid framework by Stelzl and colleagues (Grossmann et al, 2015) provides a new prism to study how tyrosine phosphorylation regulates the changes in the interactome under varying conditions. Protein-protein interaction network dynamics remain difficult to assay by most existing techniques. A kinase-dependent yeast two-hybrid framework by Stelzl and colleagues (Grossmann et al, 2015) allows analysing how tyrosine phosphorylation controls interactome dynamics under varying conditions. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.