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Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.

Publication ,  Journal Article
Gu, JJ; Lavau, CP; Pugacheva, E; Soderblom, EJ; Moseley, MA; Pendergast, AM
Published in: Sci Signal
July 17, 2012

Chemokine signaling is critical for T cell function during homeostasis and inflammation and directs T cell polarity and migration through the activation of specific intracellular pathways. Here, we uncovered a previously uncharacterized role for the Abl family tyrosine kinases Abl and Arg in the regulation of T cell-dependent inflammatory responses and showed that the Abl family kinases were required for chemokine-induced T cell polarization and migration. Our data demonstrated that Abl and Arg were activated downstream of chemokine receptors and mediated the chemokine-induced tyrosine phosphorylation of human enhancer of filamentation 1 (HEF1), an adaptor protein that is required for the activity of the guanosine triphosphatase Rap1, which mediates cell adhesion and migration. Phosphorylation of HEF1 by Abl family kinases and activation of Rap1 were required for chemokine-induced T cell migration. Mouse T cells that lacked Abl and Arg exhibited defective homing to lymph nodes and impaired migration to sites of inflammation. These findings suggest that Abl family kinases are potential therapeutic targets for the treatment of T cell-dependent immune disorders that are characterized by chemokine-mediated inflammation.

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Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

July 17, 2012

Volume

5

Issue

233

Start / End Page

ra51

Location

United States

Related Subject Headings

  • Time-Lapse Imaging
  • T-Lymphocytes
  • Signal Transduction
  • Protein-Tyrosine Kinases
  • Phosphorylation
  • Phosphoproteins
  • Mice
  • Inflammation
  • Humans
  • Guanosine Triphosphate
 

Citation

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Gu, J. J., Lavau, C. P., Pugacheva, E., Soderblom, E. J., Moseley, M. A., & Pendergast, A. M. (2012). Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1. Sci Signal, 5(233), ra51. https://doi.org/10.1126/scisignal.2002632
Gu, Jing Jin, Catherine P. Lavau, Elena Pugacheva, Erik J. Soderblom, M Arthur Moseley, and Ann Marie Pendergast. “Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.Sci Signal 5, no. 233 (July 17, 2012): ra51. https://doi.org/10.1126/scisignal.2002632.
Gu JJ, Lavau CP, Pugacheva E, Soderblom EJ, Moseley MA, Pendergast AM. Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1. Sci Signal. 2012 Jul 17;5(233):ra51.
Gu, Jing Jin, et al. “Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.Sci Signal, vol. 5, no. 233, July 2012, p. ra51. Pubmed, doi:10.1126/scisignal.2002632.
Gu JJ, Lavau CP, Pugacheva E, Soderblom EJ, Moseley MA, Pendergast AM. Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1. Sci Signal. 2012 Jul 17;5(233):ra51.

Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

July 17, 2012

Volume

5

Issue

233

Start / End Page

ra51

Location

United States

Related Subject Headings

  • Time-Lapse Imaging
  • T-Lymphocytes
  • Signal Transduction
  • Protein-Tyrosine Kinases
  • Phosphorylation
  • Phosphoproteins
  • Mice
  • Inflammation
  • Humans
  • Guanosine Triphosphate