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CUTTING EDGE |
*
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206;
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; and
Cancer Biology Program, Division of Hematology-Oncology, Department of Medicine, Beth Israel-Deaconess Medical Center, Boston, MA 02115
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-
B-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.
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