A major challenge of the post-genome era is to understand how dynamic protein-protein interactions regulate normal cell physiology and how aberrant interactions result in diseases such as cancer. The goal of this CRC is to identify, systematically, protein-protein interactions and the resultant signaling networks mediated by phosphorylation, a prevalent post-translational modification occurring on numerous regulatory proteins. We will uncover, using proteomic approaches such as peptide and protein microarrays and mass spectrometry, how changes in protein tyrosine phosphorylation and the accompanying changes in the underlying phosphorylation signaling network affect cellular state and leads to cellular transformation and metastasis of cancer.