Letter abstract
Nature Cell Biology 9, 713 - 719 (2007)
Published online: 7 May 2007 | doi:10.1038/ncb1592
The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2
Adam Mor1, Gabriele Campi2,3, Guangwei Du4, Yang Zheng5, David A. Foster5, Michael L. Dustin2,3 & Mark R. Philips1,6,7
Ras activation as a consequence of antigen receptor (T-cell receptor; TCR) engagement on T lymphocytes is required for T-cell development, selection and function. Lymphocyte function-associated antigen-1 (LFA-1) mediates lymphocyte adhesion, stabilization of the immune synapse and bidirectional signalling. Using a fluorescent biosensor we found that TCR activation with or without costimulation of CD28 led to activation of Ras only on the Golgi apparatus, whereas costimulation with LFA-1 induced Ras activation on both the Golgi and the plasma membrane. Ras activation on both compartments required RasGRP1, an exchange factor regulated by calcium and diacylglycerol (DAG), but phospholipase C (PLC) activity was required only for activation on the Golgi. Engagement of LFA-1 increased DAG levels at the plasma membrane by stimulating phospholipase D (PLD). PLD2 and phosphatidic acid phosphatase (PAP) were required for Ras activation on the plasma membrane. Thus, LFA-1 acts through PLD2 to reshape the pattern of Ras activation downstream of the TCR.
- Department of Medicine, NYU School of Medicine, New York, NY 10016, USA.
- Department of Pathology, NYU School of Medicine, New York, NY 10016, USA.
- The Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY 10016, USA.
- Department of Pharmacology, SUNY Stony Brook, NY 11794, USA.
- Department of Biological Sciences, Hunter College, City University of New York, New York, NY 10021, USA.
- Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
- Department of Pharmacology NYU School of Medicine, New York, NY 10016, USA.
Correspondence to: Mark R. Philips1,6,7 e-mail: philim01@med.nyu.edu
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