Role of the heterotrimeric G proteins in stromal-derived factor-1alpha-induced natural killer cell chemotaxis and calcium mobilization.
The CXC chemokine stromal derived factor-1alpha (SDF-1alpha) induces both the chemotaxis and calcium mobilization in IL-2-activated NK (IANK) cells. The ability of SDF-1alpha to induce IANK cell chemotaxis is inhibited upon incorporating antibodies to the alpha subunit of Go and Gq but not Gi, Gs, or Gz, whereas (Ca++)i mobilization is inhibited with anti-Go, [corrected] anti-Gq and anti-Gs, but not with any other anti-G proteins examined. Further analysis showed that antibody to phospholipase C (PLC)beta but not PLCgamma inhibited SDF-1alpha-induced (Ca++)i mobilization, suggesting that this signal is mediated by G protein coupled receptor and not by tyrosine kinase receptors. Our results are the first to show that SDF-1alpha is chemoattractant for NK cells, and that this effect is coupled to G proteins.
Maghazachi
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Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Blindern, Norway. azzam.maghazachi@basalmed.uio.no
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D007158:Immunologic Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D007376:Interleukin-2; D019204:GTP-Binding Proteins; D002118:Calcium