Article Dans Une Revue Blood Année : 2005

RGS16 is a negative regulator of SDF-1–CXCR4 signaling in megakaryocytes

Résumé

Abstract Regulators of G-protein signaling (RGS) constitute a family of proteins involved in the negative regulation of signaling through heterotrimeric G protein–coupled receptors (GPCRs). Several RGS proteins have been implicated in the down-regulation of chemokine signaling in hematopoietic cells. The chemokine stromal-cell–derived factor 1 (SDF-1) activates migration of hematopoietic progenitors cells but fails to activate mature megakaryocytes despite high levels of CXC chemokine receptor 4 (CXCR4) receptor expression in these cells. This prompted us to analyze RGS expression and function during megakaryocyte differentiation. We found that RGS16 and RGS18 mRNA expression was up-regulated during this process. Overexpressing RGS16 mRNA in the megakaryocytic MO7e cell line inhibited SDF-1–induced migration, mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) activation, whereas RGS18 overexpression had no effect on CXCR4 signaling. Knocking down RGS16 mRNA via lentiviral-mediated RNA interference increased CXCR4 signaling in MO7e cells and in primary megakaryocytes. Thus, our data reveal that RGS16 is a negative regulator of CXCR4 signaling in megakaryocytes. We postulate that RGS16 regulation is a mechanism that controls megakaryocyte maturation by regulating signals from the microenvironment.

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Dates et versions

hal-03765470 , version 1 (31-08-2022)

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Magali Berthebaud, Christel Rivière, Peggy Jarrier, Adlen Foudi, Yanyan Zhang, et al.. RGS16 is a negative regulator of SDF-1–CXCR4 signaling in megakaryocytes. Blood, 2005, 106 (9), pp.2962-2968. ⟨10.1182/blood-2005-02-0526⟩. ⟨hal-03765470⟩
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