Modulation of lysophosphatidic acid-induced Cl- currents by protein kinases A and C in the Xenopus oocyte
SCIE
SCOPUS
- Title
- Modulation of lysophosphatidic acid-induced Cl- currents by protein kinases A and C in the Xenopus oocyte
- Authors
- Kim, MJ; Lee, YS; Han, JK
- Date Issued
- 2000-02-01
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Abstract
- The roles of protein kinase C (PKC) and protein kinase A (PKA) in the regulation of lysophosphatidic acid (LPA)-induced Cl- currents in Xenopus oocytes were examined. PKC activation by phorbol 12-myristate 13-acetate (PMA) treatment completely blocked LPA-induced Cl- currents by inhibiting inositol 1,4,5-trisphosphate (IP3) elevation. This inhibitory effect of PMA on the LPA response was blocked by pretreatment of oocytes with staurosporine and 3-[N-(dimethylamino)propyl-3-indolyl]-4 (GF109203X), PKC inhibitors. In addition, treatment of oocytes with GF109203X enhanced the LPA response by increasing IP3 production. Elevation of the intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration by treating oocytes with either forskolin (FK) plus isobutylmethylxanthine (IBMX) or 2'-O-dibueyryl-cAMP (dB cAMP) reduced LPA-induced Cl- currents. The effect of activation of the cAMP pathway appears to be mediated by PKA, since treatment of oocytes with FK plus IBMX or dB cAMP enhanced PKA activity. Furthermore, the inhibitory effect of dB-cAMP on the LPA response was blocked by treatment of oocytes with N-[2-(p-bromocinnamylamino)ethyl] 5-isoquinolinesulframide-2HCl (H-89), a selective inhibitor of PKA. Both FK plus IBMX and dB-cAMP treatment reduced IF3 generation in response re, LPA stimulation Inhibition of PKA activity with H-89 or Rp-cyclic 3',5'-hydrogen phosphurothioate adenosine triethylammonium had no effect on LPA-induced Cl- currents. Finally, inhibition of the LPA response by activation of PKA was independent of extracellular Ca2+. These results demonstrate that both PKC and PKA play active roles in modulating the LPA-induced signaling pathway. (C) 1999 Elsevier Science Inc.
- Keywords
- lysophosphatidic acid; PKC; PKA; Cl- current; Ca2+; Xenopus oocyte; MEIOTIC CELL-DIVISION; HOMOLOGOUS DESENSITIZATION; RECEPTOR; PHOSPHORYLATION; ACTIVATION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/20178
- DOI
- 10.1016/S0006-2952(99)00331-7
- ISSN
- 0006-2952
- Article Type
- Article
- Citation
- BIOCHEMICAL PHARMACOLOGY, vol. 59, no. 3, page. 241 - 247, 2000-02-01
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