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Differential Effects of G Protein–Coupled Receptors on Hematopoietic Progenitor Cell Growth Depend on their Signaling Capacities
Author(s) -
XUE XINGKUI,
CAI ZHEN,
SEITZ GABRIELE,
KANZ LOTHAR,
WEISEL KATJA C.,
MÖHLE ROBERT
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1392.014
Subject(s) - microbiology and biotechnology , g protein coupled receptor , receptor , chemokine receptor , progenitor cell , biology , signal transduction , chemotaxis , chemistry , chemokine , stem cell , biochemistry
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.