Regulation of T cell activation, anxiety, and male aggression by RGS2

Antonio J. Oliveira-dos-Santos, Goichi Matsumoto, Bryan E. Snow, Donglin Bai, Frank P. Houston, Ian Q. Whishaw, Sanjeev Mariathasan, Takehiko Sasaki, Andrew Wakeham, Pamela S. Ohashi, John C. Roder, Carol A. Barnes, David P. Siderovski, Josef M. Penninger

Research output: Contribution to journalArticlepeer-review

234 Scopus citations

Abstract

Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Gα protein subunits in vitro, negatively regulating G protein-coupled receptor signaling. The physiological role of mammalian RGS proteins is largely unknown. The RGS family member rgs2 was cloned as an immediate early response gene up-regulated in T lymphocytes after activation. To investigate the role of RGS2 in vivo, we generated rgs2-deficient mice. We show that targeted mutation of rgs2 in mice leads to reduced T cell proliferation and IL-2 production, which translates in an impaired antiviral immunity in vivo. Interestingly, rgs2(-/-) mice also display increased anxiety responses and decreased male aggression in the absence of cognitive or motor deficits. RGS2 also controls synaptic development and basal electrical activity in hippocampal CA1 neurons. Thus, RGS2 plays an important role in T cell activation, synapse development in the hippocampus, and emotive behaviors.

Original languageEnglish
Pages (from-to)12272-12277
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number22
DOIs
StatePublished - 24 Oct 2000

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