Open AccessLysophosphatidic acid possesses dual action in cellproliferation.
Author(s) -
Gábor Tigyi,
David L. Dyer,
Ricardo Miledi
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.5.1908
Subject(s) - lysophosphatidic acid , pertussis toxin , second messenger system , microbiology and biotechnology , cell growth , biology , 3t3 cells , phosphatidic acid , jurkat cells , forskolin , cell culture , diacylglycerol kinase , signal transduction , g protein , biochemistry , transfection , protein kinase c , t cell , receptor , immunology , phospholipid , genetics , immune system , membrane
Lysophosphatidic acid (LPA) induces mitogenicresponses in cultured fibroblasts through a pertussis toxin-sensitive signalingpathway. In contrast, we have shown that LPA inhibits the proliferation ofSp2/0-Ag14 myeloma cells. To resolve this apparent controversy, LPA-elicitedresponses in cell proliferation and the underlying second messenger mechanismswere compared in Sp2/0-Ag14 myeloma and NIH 3T3 fibroblast cells. Theantimitogenic response was not elicited by micromolar concentrations ofphosphatidic acid, phosphatidylglycerol, or diacylglycerol. In NIH 3T3 and Sp2cells, LPA elicited an increase in inositol trisphosphate and a subsequenttransient increase in free cytoplasmic Ca2+. Unlike the mitogenic response inNIH 3T3 cells, the antimitogenic effect was not affected by pertussis toxin; onthe contrary, it was accompanied by an increase in cAMP. In Sp2 cells, cAMPanalogs, forskolin, and isobutylmethylxanthine inhibited cell proliferation andenhanced LPA action in an additive manner, suggesting that an LPA-elicitedincrease in cAMP-mediated signaling was responsible for the antimitogenicresponse. In addition to the mitogenic response in fibroblasts and theantimitogenic response in tumor cell lines, there are some cell types (JurkatT-cell lymphoma and primary astrocytes) in which LPA is ineffective in alteringcell proliferation. The cell-type-specific dual action of LPA suggests that thisendogenous lipid mediator when released from activated cells might play animportant role as a regulator, rather than a ubiquitous inducer, of cellproliferation.