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Content archived on 2024-06-18

Proteomic analysis of signaling induced by receptor tyrosine kinase endocytosis

Objective

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.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2009-IEF
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

KOBENHAVNS UNIVERSITET
EU contribution
€ 206 129,00
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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