Mass spectrometry has become one of the most rapidly evolving analytical tools to study molecular mechanisms within cellular systems. Our group is interested in protein-protein interactions and post-translational modifications which e.g. play important roles in T-cell signaling and the assembly of spliceosomes. Affinity mass spectrometry approaches are used to study modification-mediated protein interactions. We established different stable isotope labeling techniques in combination with high-accuracy and high-MS/MS capacity mass spectrometry and performed methodological studies which include attempts to improve the analysis of post-translation modification of proteins.