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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.

Original publication

DOI

10.1038/ncb1592

Type

Journal article

Journal

Nature cell biology

Publication Date

06/2007

Volume

9

Pages

713 - 719

Addresses

Department of Medicine, NYU School of Medicine, New York, NY 10016, USA.

Keywords

T-Lymphocytes, Jurkat Cells, Cell Membrane, Golgi Apparatus, Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Mice, ras Proteins, Phospholipase D, Diglycerides, Guanine Nucleotide Exchange Factors, DNA-Binding Proteins, Lymphocyte Function-Associated Antigen-1, Receptors, Antigen, T-Cell, Antigens, CD28, Cell Communication, Signal Transduction, Enzyme Activation, Type C Phospholipases