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Lysophosphatidic acid receptor responses in cells lacking the known LPA receptors
Author(s) -
Valentine William J,
Tigyi Gabor
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb44-b
Subject(s) - lysophosphatidic acid , receptor , cytoskeleton , microbiology and biotechnology , kinase , biology , mapk/erk pathway , chemistry , cell , biochemistry
The objective of this study was to characterize lysophosphatidic acid (LPA) responses in RH7777 cells and LPA1&2 double knock‐out mouse embryonic fibroblasts (dKO MEFs). Reverse‐transcription PCR was performed to profile the expression of known LPA receptors. Western blots were performed to detect MAP kinase activation. Cellular cytoskeletal changes were documented by light microscopy. Pharmacological inhibitors were used to identify signaling pathways activated by the LPA. RH7777 cells lacked mRNA for the known LPA G‐protein coupled receptors, whereas dKO MEFs contained transcripts for LPA4 but not LPA1‐3. Both cell lines had transcripts for the intracellular LPA receptor PPARγ. LPA dose‐dependently stimulated a transient activation of ERK and P38 MAP kinases in RH7777 cells and dKO MEFs that was maximal at 5 minutes after treatment. RH7777 cells and dKO MEFs underwent cytoskeletal changes in response to LPA that was characterized by rapid and transient blebbing of the plasma membrane. In RH7777 cells, blebbing was induced by 18:1 acyl‐ and alkyl‐LPA, but not by 18:0 LPA species nor by 18:1 alkyl‐glycerol. Blebbing in response to LPA was dependent upon the activities of the GTPases Rac and Rho but not PPARγ nor the trimeric G protein subunit Gαi. Our results indicate RH7777 cells and dKO MEFs contain a novel LPA receptor activity that causes blebbing of the plasma membrane and activates MAP kinase pathways. This work was supported by NIH grant HL07641‐18 and HL 61469.