HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse

Immunity. 2006 Jun;24(6):741-52. doi: 10.1016/j.immuni.2006.03.022.

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, PLCgamma1, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Actins / metabolism*
  • Animals
  • Blood Proteins / analysis
  • Blood Proteins / genetics
  • Blood Proteins / metabolism*
  • Calcium / metabolism
  • Cells, Cultured
  • Humans
  • Interleukin-2 / genetics*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Mutant Strains
  • Phospholipase C gamma / metabolism
  • Phosphorylation
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-vav / metabolism
  • Receptors, Antigen, T-Cell / agonists
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology*
  • Transcription, Genetic
  • Tyrosine / metabolism

Substances

  • Actins
  • Blood Proteins
  • HCLS1 protein, human
  • Interleukin-2
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, T-Cell
  • Vav1 protein, mouse
  • Tyrosine
  • Phospholipase C gamma
  • Calcium