The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics

Jacquelyn A. Gorman, Alexander Babich, Christopher J. Dick, Renee A. Schoon, Alexander Koenig, Timothy S. Gomez, Janis K. Burkhardt, Daniel D. Billadeau

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The Ras GTPase-activating-like protein IQGAP1 is a multimodular scaffold that controls signaling and cytoskeletal regulation in fibroblasts and epithelial cells. However, the functional role of IQGAP1 in T cell development, activation, and cytoskeletal regulation has not been investigated. In this study, we show that IQGAP1 is dispensable for thymocyte development as well as microtubule organizing center polarization and cytolytic function in CD8 + T cells. However, IQGAP1-deficient CD8 + T cells as well as Jurkat T cells suppressed for IQGAP1 were hyperresponsive, displaying increased IL-2 and IFN-γ production, heightened LCK activation, and augmented global phosphorylation kinetics after TCR ligation. In addition, IQGAP1-deficient T cells exhibited increased TCR-mediated F-actin assembly and amplified F-actin velocities during spreading. Moreover, we found that discrete regions of IQGAP1 regulated cellular activation and F-actin accumulation. Taken together, our data suggest that IQGAP1 acts as a dual negative regulator in T cells, limiting both TCR-mediated activation kinetics and F-actin dynamics via distinct mechanisms.

Original languageEnglish (US)
Pages (from-to)6135-6144
Number of pages10
JournalJournal of Immunology
Volume188
Issue number12
DOIs
StatePublished - Jun 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gorman, J. A., Babich, A., Dick, C. J., Schoon, R. A., Koenig, A., Gomez, T. S., Burkhardt, J. K., & Billadeau, D. D. (2012). The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics. Journal of Immunology, 188(12), 6135-6144. https://doi.org/10.4049/jimmunol.1103487