Signalisation cellulaire et formation de complexes protéiques lors de l'étirement des cardiomyocytes de rats nouveaux-nés

Nicolas Duquesnes 1
1 IMRB
IMRB - Institut Mondor de recherche biomédicale
Abstract : Cardiomyocyte stretch is a major determinant of ventricular hypertrophy. It stimulates numerous signalling pathways leading to the Mitogen Activated Protein kinases (MAPK) activation. The objective of this thesis was to evaluate the molecular events involved in MAPK ERK and JNK activations during stretch. We studied these pathways by 2 different approaches. We analysed the role of several pivotal proteins involved in ERK and JNK activations and next we evaluated the molecular interactions between different signalling pathways by protein complexes formation induced by stretch and necessary for protein activations. We show that 2 tyrosine Kinases, the Epidermal Growth Factor Receptor (EGFR) and the Proline-rich tyrosine kinase 2 (Pyk2) are necessary for ERK and JNK activations respectively during stretch with a possible involvement of the small G protein Ras. MAPK and PI3/Akt pathways are generally considered independent but we show that ERK activation is PI3K/Akt dependent during stretch. Thus, we demonstrate that 2 other pathways are associated since PKC and calcineurin form a complex necessary for PKC activation and translocation. This study of signalling pathways and protein interactions sheds a new light on intracellular pathways leading to MAPK activation and may have implications for the development of new drugs in the management of cardiac hypertrophy and failure
Document type :
Theses
Agricultural sciences. Université Paris-Est, 2008. French. <NNT : 2008PEST0015>


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Nicolas Duquesnes. Signalisation cellulaire et formation de complexes protéiques lors de l'étirement des cardiomyocytes de rats nouveaux-nés. Agricultural sciences. Université Paris-Est, 2008. French. <NNT : 2008PEST0015>. <tel-00842230>

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