Adenosine-stimulated adrenal steroidogenesis involves the adenosine A2A and A2B receptors and the Janus kinase 2–mitogen-activated protein kinase kinase–extracellular signal-regulated kinase signaling pathway

2008 ◽  
Vol 40 (12) ◽  
pp. 2815-2825 ◽  
Author(s):  
Yung-Chia Chen ◽  
Shih-Horng Huang ◽  
Seu-Mei Wang
Keyword(s):  
Protein Kinase ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Adrenal Steroidogenesis ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Adenosine A2a ◽  
Kinase Signaling Pathway ◽  
Protein Kinase Kinase

scholarly journals Activation of mitogen-activated protein kinase kinase (MEK)/extracellular signal–regulated kinase (ERK) signaling pathway is involved in myeloid lineage commitment

Blood ◽  
2007 ◽  
Vol 110 (5) ◽  
pp. 1420-1428 ◽  
Author(s):  
Chia-Lin Hsu ◽  
Kazu Kikuchi ◽  
Motonari Kondo
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Lineage Commitment ◽  
Myeloid Differentiation ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

Abstract Common lymphoid progenitors (CLPs) are lymphoid-lineage-committed progenitor cells. However, they maintain a latent myeloid differentiation potential that can be initiated by stimulation with interleukin-2 (IL-2) via ectopically expressed IL-2 receptors. Although CLPs express IL-7 receptors, which share the common γ chain with IL-2 receptors, IL-7 cannot initiate lineage conversion in CLPs. In this study, we demonstrate that the critical signals for initiating lineage conversion in CLPs are delivered via IL-2 receptor β (IL-2Rβ) intracellular domains. Fusion of the A region of the IL-2Rβ cytoplasmic tail to IL-7Rα enables IL-7 to initiate myeloid differentiation in CLPs. We found that Shc, which associates with the A region, mediates lineage conversion signals through the mitogen activated protein kinase (MAPK) pathway. Because mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitors completely blocked IL-2-mediated lineage conversion, MAPK activation, specifically via the MEK/ERK pathway, is critically involved in the initiation of this event. Furthermore, formation of granulocyte/macrophage (GM) colonies by hematopoietic stem cells, but not by common myeloid progenitors (CMPs), was severely reduced in the presence of MEK/ERK inhibitors. These results demonstrate that activation of MEK/ERK plays an important role in GM lineage commitment.

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