CORDIS
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Proteomic analysis of signaling induced by receptor tyrosine kinase endocytosis

Project information

Grant agreement ID: 252594

Status

Closed project

  • Start date

    1 March 2010

  • End date

    29 February 2012

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 206 129

  • EU contribution

    € 206 129

Coordinated by:

KOBENHAVNS UNIVERSITET

Denmark

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.
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Coordinator

KOBENHAVNS UNIVERSITET

Address

Norregade 10
1165 Kobenhavn

Denmark

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 206 129

Administrative Contact

Ivan Kristoffersen (Mr.)

Project information

Grant agreement ID: 252594

Status

Closed project

  • Start date

    1 March 2010

  • End date

    29 February 2012

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 206 129

  • EU contribution

    € 206 129

Coordinated by:

KOBENHAVNS UNIVERSITET

Denmark