RGS16 is a negative regulator of SDF-1-CXCR4 signaling in megakaryocytes.
Blood
; 106(9): 2962-8, 2005 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-15998835
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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Megacariocitos
/
Transducción de Señal
/
Proteínas
/
Receptores CXCR4
/
Quimiocinas CXC
/
Proteínas RGS
Límite:
Humans
Idioma:
En
Revista:
Blood
Año:
2005
Tipo del documento:
Article
País de afiliación:
Francia