Journal
MOLECULAR CELL
Volume 40, Issue 5, Pages 798-809Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2010.11.007
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Funding
- National Institutes of Health [RO1AI078980, PO1AI072677]
- American Cancer Society [RSG-06-172-01-LIB]
- Johns Hopkins University Institute for Cell Engineering
- Ruth L. Kirschstein National Research Service Award [F31AG031689]
- Sidney Kimmel Foundation for Cancer Research
- Rita Allen Foundation
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T cell receptor (TCR) signaling to NF-kappa B is required for antigen-induced T cell activation. We conducted an expression-cloning screen for modifiers of CARD11, a critical adaptor in antigen receptor signaling, and identified the kinesin-3 family member GAKIN as a CARD11 inhibitor. GAKIN negatively regulates TCR signaling to NE-kappa B, associates with CARD11 in a signal-dependent manner and can compete with the required signaling protein, Bcl10, for association. In addition, GAKIN dynamically localizes to the immunological synapse and regulates the redistribution of CARD11 from the central region of the synapse to a distal region. We propose that CARD11 scaffold function and occupancy at the center of the synapse are negatively regulated by GAKIN to tune the output of antigen-receptor signaling.
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