The receptor tyrosine kinases KIT and FLT3 are both important regulators of development and maintenance of a number of different cell types. Deregulation of these receptors by mutations has been implicated in various human malignancies, including akut myeloid leukemia and melanoma. The signaling pathways activated by the oncogenic mutants are to some extent unique and different from wild-type receptor signaling. These molecules are potential novel targets for pharmacological intervention. By a broad mass spectrometry based approach on whole cells we are in the process of identifying additional such proteins and their phosphorylation status. Finally, patients with certain subtypes of malignant melanoma carry activating mutations in KIT that is driving the disease. Given the functional relation between KIT and the transcription factor MITF, we are investigating the molecular mechanisms behind the KIT-mediated regulation of MITF.