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Study of the tissue-specific interactome of the GRK2 node involved in insulin resistance and obesity: pathological repercussions

17th national competition for scientific and technical research

Interactome: pathological implications

Senior Researcher : Cristina Murga Montesinos

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Research Centre or Institution : Centro de Biología Molecular "Severo Ochoa". CSIC-Universidad Autónoma de Madrid


Protein GRK2 ("G protein-bound receptor kinase 2") is a central and strategic node in cell signalling networks in different tissues. Recently GRK2 has been shown to be able to regulate different families of membrane receptors and to interact with important signalling proteins, which could explain the role of GRK2 in different pathologies. Our research team has discovered that GRK2 expression increases in situations involving insulin resistance and obesity, and has also identified new physical and functional interactions of GRK2 with proteins that are extremely important for pathologies, such as IRS1 and p38MAPK, among others.

The main aims of this project are: 1.- To characterise the relevant interactome of GRK2 that is specific to tissues and cell types (adipose, pancreas, liver, macrophages) involved in the genesis or development of insulin resistance and obesity. 2.- To study which changes in the aforementioned interactome underlie the development of lipotoxicity, and inflammatory processes in these contexts. 3.- To evaluate the function impact of the changes in GRK2 levels detected in the aforementioned pathologies on the selection of its interactome in each tissue, and 4.- To analyse the possibility of modulating the interactome or the expression of GRK2 as a new therapeutic strategy.

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