Source:http://linkedlifedata.com/resource/pubmed/id/19295169
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2009-5-4
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pubmed:abstractText |
The activation of Kv1.3 potassium channel has obligatory roles in immune responses of T lymphocytes. Stromal cell-derived factor-1alpha (SDF-1alpha) binds to C-X-C chemokine receptor type 4, activates phosphoinositide 3-kinase, and plays essential roles in cell migration of T lymphocytes. In this study, the effects of phosphoinositides and SDF-1alpha on Kv1.3 current activity were examined in the Jurkat T cell line using whole cell patch-clamp techniques. The internal application of 10 microM phosphatidylinositol 4,5-bisphosphate (PIP(2)) or 10 microM phosphatidylinositol-3,4,5-trisphosphate (PIP(3)) significantly reduced Kv1.3 current, but that of 10 microM phosphatidylinositol-4-monophosphate (PIP) did not. The coapplication of 10 microg/ml anti-PIP(3) antibody with PIP(2) from the pipette did not change the reduction of Kv1.3 current by PIP(2), but the coapplication of the antibody with PIP(3) eliminated the reduction. The heat-inactivated anti-PIP(3) antibody had no effect on PIP(3)-induced inhibition. These results suggest that PIP(2) per se can reduce Kv1.3 current as well as PIP(3). External application of 1 muM Akt-kinase inhibitor VIII did not reverse the effect of intracellular PIP(3). External application of 10 and 30 ng/ml SDF-1alpha significantly reduced Kv1.3 current. Internal application of anti-PIP(3) antibody reversed the SDF-1alpha-induced reduction. These results suggest that, in Jurkat T cells, PIP(2), PIP(3), and SDF-1alpha reduce Kv1.3 channel activity and that the reduction by SDF-1alpha may be mediated by the enhancement of PIP(3) production. These novel inhibitory effects of phosphoinositides and SDF-1alpha on Kv1.3 current may have a significant function as a downregulation mechanism of Kv1.3 activity for the maintenance of T lymphocyte activation in immune responses.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/CXCL12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL12,
http://linkedlifedata.com/resource/pubmed/chemical/Kv1.3 Potassium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 4,5-Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/phosphatidylinositol...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0363-6143
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C1079-85
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19295169-Antibodies,
pubmed-meshheading:19295169-Chemokine CXCL12,
pubmed-meshheading:19295169-Down-Regulation,
pubmed-meshheading:19295169-Humans,
pubmed-meshheading:19295169-Ion Channel Gating,
pubmed-meshheading:19295169-Jurkat Cells,
pubmed-meshheading:19295169-Kv1.3 Potassium Channel,
pubmed-meshheading:19295169-Membrane Potentials,
pubmed-meshheading:19295169-Patch-Clamp Techniques,
pubmed-meshheading:19295169-Phosphatidylinositol 4,5-Diphosphate,
pubmed-meshheading:19295169-Phosphatidylinositol Phosphates,
pubmed-meshheading:19295169-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19295169-T-Lymphocytes
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pubmed:year |
2009
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pubmed:articleTitle |
Inhibition of Kv1.3 potassium current by phosphoinositides and stromal-derived factor-1alpha in Jurkat T cells.
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pubmed:affiliation |
Dept. of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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