RasGRF2, a guanosine nucleotide exchange factor for Ras GTPases, participates in T-cell signaling responses.

Abstract:

:The Ras pathway is critical for the development and function of T lymphocytes. The stimulation of this GTPase in T cells occurs primarily through the Vav1- and phospholipase C-gamma1-dependent activation of RasGRP1, a diacylglycerol-responsive Ras GDP/GTP exchange factor. Here, we show that a second exchange factor, RasGRF2, also participates in T-cell signaling. RasGRF2 is expressed in T cells, translocates to immune synapses, activates Ras, and stimulates the transcriptional factor NF-AT (nuclear factor of activated T cells) through Ras- and phospholipase C-gamma1-dependent routes. T-cell receptor-, Vav1-, and Ca2+-elicited pathways synergize with RasGRF2 for NF-AT stimulation. The analysis of RasGRF2-deficient mice indicates that this protein is required for the induction of bona fide NF-AT targets such as the cytokines tumor necrosis factor alpha and interleukin 2, while it plays minor roles in Ras activation itself. The comparison of lymphocytes from Vav1-/-, Rasgrf2-/-, and Vav1-/-; Rasgrf2-/- mice demonstrates that the RasGRF2 pathway cooperates with the Vav1/RasGRP1 route in the blasting transformation and proliferation of mature T cells. These results identify RasGRF2 as an additional component of the signaling machinery involved in T-cell receptor- and NF-AT-mediated immune responses.

journal_name

Mol Cell Biol

authors

Ruiz S,Santos E,Bustelo XR

doi

10.1128/MCB.00912-07

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

8127-42

issue

23

eissn

0270-7306

issn

1098-5549

pii

MCB.00912-07

journal_volume

27

pub_type

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