| Autor: |
Leon, Carlos M.M.P., Barbosa, Christiano M.V., Justo, Giselle Z., Borelli, Primavera, Junior, José Dias Resende, de Oliveira, José S.R., Ferreira, Alice T., Paredes-Gamero, Edgar J. |
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| Zdroj: |
Journal of Cellular Physiology; Jul2011, Vol. 226 Issue 7, p1780-1792, 13p, 1 Diagram, 8 Graphs |
| Abstrakt: |
Even though the involvement of intracellular Ca () in hematopoiesis has been previously demonstrated, the relationship between signaling and cytokine-induced intracellular pathways remains poorly understood. Herein, the molecular mechanisms integrating Ca signaling with the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in primary murine and human hematopoietic stem/progenitor cells stimulated by IL-3 and GM-CSF were studied. Our results demonstrated that IL-3 and GM-CSF stimulation induced increased inositol 1,4,5-trisphosphate (IP) levels and release in murine and human hematopoietic stem/progenitor cells. In addition, signaling inhibitors, such as inositol 1,4,5-trisphosphate receptor antagonist (2-APB), PKC inhibitor (GF109203), and CaMKII inhibitor (KN-62), blocked phosphorylation of MEK activated by IL-3 and GM-CSF, suggesting the participation of Ca-dependent kinases in MEK activation. In addition, we identify phospholipase Cγ2 (PLCγ2) as a PLCγ responsible for the induction of Ca release by IL-3 and GM-CSF in hematopoietic stem/progenitor cells. Furthermore, the PLCγ inhibitor U73122 significantly reduced the numbers of granulocyte-macrophage colony-forming units after cytokine stimulation. Similar results were obtained in both murine and human hematopoietic stem/progenitor cells. Taken together, these data indicate a role for PLCγ2 and Ca signaling through the modulation of MEK in both murine and human hematopoietic stem/progenitor cells. J. Cell. Physiol. 226: 1780-1792, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR] |
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