Differential effects of G protein coupled receptors on hematopoietic progenitor cell growth depend on their signaling capacities
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Differential effects of G protein coupled receptors on hematopoietic progenitor cell growth depend on their signaling capacities. / Xue, Xingkui; Cai, Zhen; Seitz, Gabriele; Kanz, Lothar; Weisel, Katja C; Möhle, Robert.
in: ANN NY ACAD SCI, Jahrgang 1106, 06.2007, S. 180-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung
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TY - JOUR
T1 - Differential effects of G protein coupled receptors on hematopoietic progenitor cell growth depend on their signaling capacities
AU - Xue, Xingkui
AU - Cai, Zhen
AU - Seitz, Gabriele
AU - Kanz, Lothar
AU - Weisel, Katja C
AU - Möhle, Robert
PY - 2007/6
Y1 - 2007/6
N2 - We have shown that CD34(+) hematopoietic progenitor and stem cells (HPCs) consistently express several G protein-coupled receptors (GPCRs): the chemokine receptor CXCR4, the cysteinyl-leukotriene receptor cysLT1, and receptors for sphingosine 1-phosphate (S1P), particularly S1P1. These GPCRs differentially mediate chemotactic, adhesive, and proliferative responses in HPCs. To elucidate the diversity of the responses observed, we compared their signaling capacities in CD34(+) cells. In primary CD34(+) progenitors, the strongest effects on calcium signaling (intracellular calcium fluxes) were mediated by cysLT1. Analyses in CD34(+) cell lines revealed that calcium signaling induced by cysLT1 was only partially inhibited by pertussis toxin (PTX), while responses induced by CXCR4 and S1P receptors were completely blocked. These findings indicate that cysLT1 signals via Gi and Gq proteins, while CXCR4 and also S1P receptors (e.g., S1P1) only induce Gi protein-mediated effects. By analysis of downstream signaling, we could provide further evidence that combined activation of PTX-insensitive (Gq-mediated) and PTX-sensitive (Gi-mediated) pathways by cysLT1 may explain the strong and broad effects of cysteinyl-leukotrienes in early hematopoietic cells, while signaling of CXCR4 and S1P1 solely depends on Gi proteins, resulting in effects mainly restricted to migration and adhesion.
AB - We have shown that CD34(+) hematopoietic progenitor and stem cells (HPCs) consistently express several G protein-coupled receptors (GPCRs): the chemokine receptor CXCR4, the cysteinyl-leukotriene receptor cysLT1, and receptors for sphingosine 1-phosphate (S1P), particularly S1P1. These GPCRs differentially mediate chemotactic, adhesive, and proliferative responses in HPCs. To elucidate the diversity of the responses observed, we compared their signaling capacities in CD34(+) cells. In primary CD34(+) progenitors, the strongest effects on calcium signaling (intracellular calcium fluxes) were mediated by cysLT1. Analyses in CD34(+) cell lines revealed that calcium signaling induced by cysLT1 was only partially inhibited by pertussis toxin (PTX), while responses induced by CXCR4 and S1P receptors were completely blocked. These findings indicate that cysLT1 signals via Gi and Gq proteins, while CXCR4 and also S1P receptors (e.g., S1P1) only induce Gi protein-mediated effects. By analysis of downstream signaling, we could provide further evidence that combined activation of PTX-insensitive (Gq-mediated) and PTX-sensitive (Gi-mediated) pathways by cysLT1 may explain the strong and broad effects of cysteinyl-leukotrienes in early hematopoietic cells, while signaling of CXCR4 and S1P1 solely depends on Gi proteins, resulting in effects mainly restricted to migration and adhesion.
KW - Antigens, CD34
KW - Calcium
KW - Calcium Signaling
KW - Cell Line
KW - Cell Proliferation
KW - Focal Adhesion Kinase 2
KW - Gene Expression Regulation
KW - Hematopoietic Stem Cells
KW - Humans
KW - Lysophospholipids
KW - Models, Biological
KW - Pertussis Toxin
KW - Phosphorylation
KW - Signal Transduction
KW - Sphingosine
KW - Time Factors
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1196/annals.1392.014
DO - 10.1196/annals.1392.014
M3 - SCORING: Journal article
C2 - 17360805
VL - 1106
SP - 180
EP - 189
JO - ANN NY ACAD SCI
JF - ANN NY ACAD SCI
SN - 0077-8923
ER -