Lipid Phosphate Phosphatase-1 and Ca2+ Control Lysophosphatidate Signaling through EDG-2 Receptors
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Post-publication record
- Nature
- Retraction
- Reason
- Falsification/Fabrication of Data;Investigation by Company/Institution;Investigation by ORI;Misconduct - Official Investigation(s) and/or Finding(s);Misconduct by Author;Results Not Reproducible;
- Date
- 9/26/2003 0:00
- Flagged by OpenAlex?
- Yes
Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.
Abstract
The serum-derived phospholipid growth factor, lysophosphatidate (LPA), activates cells through the EDG family of G protein-coupled receptors. The present study investigated mechanisms by which dephosphorylation of exogenous LPA by lipid phosphate phosphatase-1 (LPP-1) controls cell signaling. Overexpressing LPP-1 decreased the net specific cell association of LPA with Rat2 fibroblasts by approximately 50% at 37 degrees C when less than 10% of LPA was dephosphorylated. This attenuated cell activation as indicated by diminished responses, including cAMP, Ca(2+), activation of phospholipase D and ERK, DNA synthesis, and cell division. Conversely, decreasing LPP-1 expression increased net LPA association, ERK stimulation, and DNA synthesis. Whereas changing LPP-1 expression did not alter the apparent K(d) and B(max) for LPA binding at 4 degrees C, increasing Ca(2+) from 0 to 50 micrometer increased the K(d) from 40 to 900 nm. Decreasing extracellular Ca(2+) from 1.8 mm to 10 micrometer increased LPA binding by 20-fold, shifting the threshold for ERK activation to the nanomolar range. Hence the Ca(2+) dependence of the apparent K(d) values explains the long-standing discrepancy of why micromolar LPA is often needed to activate cells at physiological Ca(2+) levels. In addition, the work demonstrates that LPP-1 can regulate specific LPA association with cells without significantly depleting bulk LPA concentrations in the extracellular medium. This identifies a novel mechanism for controlling EDG-2 receptor activation.
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The record
- Venue
- Journal of Biological Chemistry
- Topic
- Sphingolipid Metabolism and Signaling
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- University of Alberta
- Funders
- National Heart, Lung, and Blood InstituteNational Institutes of HealthU.S. Public Health ServiceMedical Research Council CanadaFondation pour la Recherche MédicaleMedical Research CouncilAmerican Heart Association
- Keywords
- ReceptorPhosphataseBiochemistryPhosphateChemistryEnzymeBiology
- Has abstract in OpenAlex
- yes