Science  14 Jan 2005:
Vol. 307, Issue 5707, pp. 206
DOI: 10.1126/science.307.5707.206b

In the Report “Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A” by Kabarowski et al. (1), we concluded that the lysolipid lysophosphatidylcholine (LPC) and a related molecule, sphingosylphosphorylcholine (SPC), directly bound to and served as agonists of the G protein-coupled receptor G2A. Concerns about the reproducibility of portions of the data lead us to retract this paper.

Critical data in the paper showed direct and specific binding of radiolabeled LPC or SPC to G2A in cell homogenates. The primary data generated by Dr. Zhu for these binding studies are not available for evaluation. During investigation of engineered point mutants of the G2A receptor, we were unable to repeat these radiolabeled ligand-binding studies following similar protocols. Alternative protocols with purified membrane fractions (2, 3) expressing high levels of the G2A receptor or whole-cell-based radioligand binding studies (46) also failed to establish direct G2A binding. This calls into question the major conclusion that LPC and SPC are direct ligands for G2A.

In attempts to reproduce LPC stimulation of intracellular calcium responses, only 50% of single MCF 10A cells expressing G2A responded to LPC in single-cell assays identical to those originally employed. Only about half of these gave robust responses similar to those shown in the Science paper. Similar assays of intracellular calcium release using bulk cell populations failed to detect any reproducible G2A-mediated response to LPC. Data generated by Dr. Kabarowski demonstrating cellular migration dependent on LPC addition and G2A receptor expression have been reproduced and extended in independent work (79). We believe these data to be accurate and reproducible and therefore conclude that G2A is an effector of LPC action in certain cell-types. However, these data cannot distinguish between a direct action of the lysolipid on the receptor and an indirect action in which the lysolipid modifies another receptor or process that in turn regulates the G2A receptor.

We sincerely regret the confusion that this paper may have caused for the readers of Science.


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