Research Article
The linoleic acid derivative DCP-LA selectively activates PKC-ɛ, possibly binding to the phosphatidylserine binding site

https://doi.org/10.1194/jlr.M500329-JLR200Get rights and content
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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 μM) 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-ɛ. Furthermore, DCP-LA activated PKC in HEK-293 cells that was inhibited by the small, interfering RNA against PKC-ɛ. In the cell-free PKC assay, of the nine isozymes examined here, DCP-LA most strongly activated PKC-ɛ, 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-γ, a conventional PKC, but to a much lesser extent compared with that for PKC-ɛ, by a mechanism distinct from PKC-ɛ activation. Thus, DCP-LA serves as a selective activator of PKC-ɛ, possibly by binding to the phosphatidylserine binding site on PKC-ɛ. These results may provide fresh insight into lipid signaling in PKC activation.

8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid
protein kinase C-ɛ
protein kinase C-γ

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Published, JLR Papers in Press, March 6, 2006.

Abbreviations

  1. ACh, acetylcholine

  2. CaMKII, Ca2+/calmodulin-dependent protein kinase II

  3. DCP-LA, 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid

  4. dNTP, deoxynucleoside triphosphate

  5. MALDI-TOF MS, matrix-assisted laser desorption ionization time-of-flight mass spectrometry

  6. MW, molecular weight

  7. PKA, protein kinase A

  8. PKC, protein kinase C

  9. PMA, phorbol 12-myristate 13-acetate

  10. siRNA, small interfering RNA