Reference - Detail
| RRC ID | 42576 |
|---|---|
| Author | Kanno T, Yamamoto H, Yaguchi T, Hi R, Mukasa T, Fujikawa H, Nagata T, Yamamoto S, Tanaka A, Nishizaki T. |
| Title | The linoleic acid derivative DCP-LA selectively activates PKC-epsilon, possibly binding to the phosphatidylserine binding site. |
| Journal | J Lipid Res |
| Abstract |
This study examined the effect of 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a newly synthesized linoleic acid derivative with cyclopropane rings instead of cis-double bonds, on protein kinase C (PKC) activity. In the in situ PKC assay with reverse-phase high-performance liquid chromatography, DCP-LA significantly activated PKC in PC-12 cells in a concentration-dependent (10 nM-100 microM) manner, with the maximal effect at 100 nM, and the DCP-LA effect was blocked by GF109203X, a PKC inhibitor, or a selective inhibitor peptide of the novel PKC isozyme PKC-epsilon. Furthermore, DCP-LA activated PKC in HEK-293 cells that was inhibited by the small, interfering RNA against PKC-epsilon. In the cell-free PKC assay, of the nine isozymes examined here, DCP-LA most strongly activated PKC-epsilon, with >7-fold potency over other PKC isozymes, in the absence of dioleoyl-phosphatidylserine and 1,2-dioleoyl-sn-glycerol; instead, the DCP-LA action was inhibited by dioleoyl-phosphatidylserine. DCP-LA also activated PKC-gamma, a conventional PKC, but to a much lesser extent compared with that for PKC-epsilon, by a mechanism distinct from PKC-epsilon activation. Thus, DCP-LA serves as a selective activator of PKC-epsilon, possibly by binding to the phosphatidylserine binding site on PKC-epsilon. These results may provide fresh insight into lipid signaling in PKC activation. |
| Volume | 47(6) |
| Pages | 1146-56 |
| Published | 2006-6-1 |
| DOI | 10.1194/jlr.M500329-JLR200 |
| PII | S0022-2275(20)33213-2 |
| PMID | 16520488 |
| MeSH | Animals Base Sequence Binding Sites Caprylates / metabolism Caprylates / pharmacology* Cell Line Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Humans Isoenzymes / antagonists & inhibitors Isoenzymes / genetics Isoenzymes / metabolism Linoleic Acids / chemistry Linoleic Acids / metabolism Linoleic Acids / pharmacology PC12 Cells Phosphatidylserines / chemistry Phosphatidylserines / metabolism* Phosphatidylserines / pharmacology Protein Kinase C / antagonists & inhibitors Protein Kinase C / genetics Protein Kinase C / metabolism Protein Kinase C-epsilon / antagonists & inhibitors Protein Kinase C-epsilon / genetics Protein Kinase C-epsilon / metabolism* RNA, Small Interfering / genetics Rats Reverse Transcriptase Polymerase Chain Reaction Substrate Specificity |
| IF | 4.483 |
| Times Cited | 62 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 57 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | |