Objectif
Stimulated Receptor Tyrosine Kinases (RTKs) regulate several key cellular processes, such as cell proliferation, differentiation, migration and transformation, by activating specific intracellular signaling pathways. Endocytosis, the process by which cells internalize and sort RTKs for either degradation or recycling, is a potent regulator of signal transduction specificity and cellular outcomes. Several RTKs have been shown to escape from the canonical degradative route under certain conditions, resulting in signaling amplification - which often results in tumorigenesis. In particular, EGFR and FGFRs follow opposite endocytic routes upon stimulation by different ligands. This application focuses on EGFR and FGFRs as model systems to define signaling cascades that are specifically regulated by the different endocytic pathways. We will integrate an unbiased data-driven approach consisting of quantitative proteomics, based on high-resolution mass-spectrometry in combination with proteome-wide metabolic incorporation of stable isotopes, followed by proper functional assays to validate the results. This system biology approach will shed light on some previously uncharacterized aspects of RTK signaling regulation at the whole-cell level, gaining insights into the molecular mechanisms underlying endocytosis-driven cellular responses. Since aberrant RTK signaling is a hallmark of various diseases, such as many cancers, the implications of our studies extend beyond basic research, offering the opportunity to identify novel therapeutic targets, e.g. for the development of anti-cancer drugs. These objectives are part of European research’s efforts to elucidate physiological processes, search for pathogenic events and novel targets and contribute to the technological progress of protein research.
Champ scientifique
Thème(s)
Appel à propositions
FP7-PEOPLE-2009-IEF
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Régime de financement
MC-IEF - Intra-European Fellowships (IEF)Coordinateur
1165 Kobenhavn
Danemark