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Régulation d'une nouvelle GAP de Rho, ARHGAP19, dans la division des lymphocytes T humains et rôle dans l'hématopoièse murine

Abstract : The team identified a new GAP of RhoA, ARHGAP19, mostly expressed in the hematopoietic system. The project consisted in studying the regulation of this protein in human T lymphocytes. For this, the analyzes focused on the phosphorylation of ARHGAP19 and on its localization during the division of the T lymphocytes. ARHGAP19 is phosphorylated by the effector of RhoA, the protein kinase ROCK, on the Serine 422 and by the protein CDK1 mitotic kinase on Threonines 404 and 476. ROCK phosphorylation allows ARHGAP19 to interact with the 14-3-3 family of proteins that protects it from dephosphorylation that occur during cell division. All phosphorylations are essential for regulating the cellular localization of ARHGAP19 and contribute to correct cell division. Indeed, in the absence of phosphorylation, defects are observed during cytodiérèse resulting in the formation of multinucleate cells.In addition, deregulation of RhoGTPases, such as the absence of GAP, are now highlighted in cancers. This is why we generated arhgap19 KO mice to study the consequences of the absence of the gene coding for ARHGAP19, in the murine hematopoietic system. All progenitor and mature cells involved in murine hematopoiesis were analyzed. By this model of conditional invalidation of arhgap19, no major role of the protein has been demonstrated but the results suggest an involvement at different stages of hematopoietic differentiation and an impact on all populations of this system.
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Submitted on : Tuesday, April 10, 2018 - 2:50:08 PM
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Claire Marceaux. Régulation d'une nouvelle GAP de Rho, ARHGAP19, dans la division des lymphocytes T humains et rôle dans l'hématopoièse murine. Biochimie, Biologie Moléculaire. Université Paris Saclay (COmUE), 2018. Français. ⟨NNT : 2018SACLS046⟩. ⟨tel-01762918⟩

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