HS1 Functions as an Essential Actin-Regulatory Adaptor Protein at the Immune Synapse

Timothy S. Gomez, Sean D. McCarney, Esteban Carrizosa, Christine M. Labno, Erin O. Comiskey, Jeffrey C. Nolz, Peimin Zhu, Bruce D. Freedman, Marcus R. Clark, David J. Rawlings, Daniel D. Billadeau, Janis K. Burkhardt

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

HS1, the leukocyte-specific homolog of cortactin, regulates F-actin in vitro and is phosphorylated in response to TCR ligation, but its role in lymphocyte activation has not been addressed. We demonstrate that HS1-deficient T cells fail to accumulate F-actin at the immune synapse (IS) and, upon TCR ligation, form actin-rich structures that are disordered and unstable. Early TCR activation events are intact in these cells, but Ca2+ influx and IL-2 gene transcription are defective. Importantly, HS1 tyrosine phosphorylation is required for its targeting to the IS and for its function in regulating actin dynamics and IL-2 promoter activity. Phosphorylation also links HS1 to multiple signaling proteins, including Lck, PLCγ1, and Vav1, and is essential for the stable recruitment of Vav1 to the IS. Taken together, our studies show that HS1 is indispensable for signaling events leading to actin assembly and IL-2 production during T cell activation.

Original languageEnglish (US)
Pages (from-to)741-752
Number of pages12
JournalImmunity
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • MOLIMMUNO
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'HS1 Functions as an Essential Actin-Regulatory Adaptor Protein at the Immune Synapse'. Together they form a unique fingerprint.

  • Cite this

    Gomez, T. S., McCarney, S. D., Carrizosa, E., Labno, C. M., Comiskey, E. O., Nolz, J. C., Zhu, P., Freedman, B. D., Clark, M. R., Rawlings, D. J., Billadeau, D. D., & Burkhardt, J. K. (2006). HS1 Functions as an Essential Actin-Regulatory Adaptor Protein at the Immune Synapse. Immunity, 24(6), 741-752. https://doi.org/10.1016/j.immuni.2006.03.022