Cutting edge: Gab2 mediates an inhibitory phosphatidylinositol 3'-kinase pathway in T cell antigen receptor signaling

J. C. Pratt, V. E. Igras, H. Maeda, S. Baksh, E. W. Gelfand, S. J. Burakoff, B. G. Neel, H. Gu

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Phosphatidylinositol 3'-kinase (PI3K) is a key component of multiple signaling pathways, where it typically promotes survival, proliferation, and/or adhesion. Here, we show that in TCR signaling, the scaffolding adapter Gab2 delivers an inhibitory signal via PI3K. Overexpression of Gab2 in T cell lines inhibits TCR-evoked activation of the IL-2 promoter, blocking NF-AT- and NF-κB-directed transcription. Inhibition is abrogated by mutating the Gab2 p85-binding sites, by treatment with PI3K inhibitors or by cotransfection of phosphatase homolog of tensin. Our findings provide the first evidence of a negative function for a scaffolding adapter in T cells and identify Gab2/PI3K-containing complexes as novel regulators of TCR signaling.

Original languageEnglish
Pages (from-to)4158-4163
Number of pages6
JournalJournal of Immunology
Volume165
Issue number8
DOIs
StatePublished - 15 Oct 2000
Externally publishedYes

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