STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease Journal Article

Authors: Lu, S. X.; Alpdogan, O.; Lin, J.; Balderas, R.; Campos-Gonzalez, R.; Wang, X.; Gao, G. J.; Suh, D.; King, C.; Chow, M.; Smith, O. M.; Hubbard, V. M.; Bautista, J. L.; Cabrera-Perez, J.; Zakrzewski, J. L.; Kochman, A. A.; Chow, A.; Altan-Bonnet, G.; van den Brink, M. R. M.
Article Title: STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease
Abstract: Graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation, and donor T cells are indispensable for GVHD. Current therapies have limited efficacy, selectivity, and high toxicities. We used a novel flow cytometry technique for the analysis of intracellular phosphorylation events in single cells in murine BMT models to identify and validate novel GVHD drug targets.1-7 This method circumvents the requirement for large numbers of purified cells, unlike western blots. We defined a signaling profile for alloactivated T cells in vivo and identified the phosphorylation of ERK1/2 and STAT-3 as important events during T-cell (allo)activation in GVHD. We establish that interference with STAT-3 phosphorylation can inhibit T-cell activation and proliferation in vitro and GVHD in vivo. This suggests that phospho-specific flow cytometry is useful for the identification of promising drug targets, and ERK1/2 and STAT-3 phosphorylation in alloactivated T cells may be important for GVHD. © 2008 by The American Society of Hematology.
Keywords: controlled study; protein phosphorylation; transplantation, homologous; unclassified drug; nonhuman; flow cytometry; cd8+ t lymphocyte; cell proliferation; t lymphocyte; t-lymphocytes; mouse; animal; metabolism; animals; mice; stat3 protein; animal experiment; animal model; allogenic bone marrow transplantation; in vivo study; in vitro study; phosphorylation; immunology; lymphocyte activation; cd4+ t lymphocyte; western blotting; cell subpopulation; graft versus host reaction; mitogen activated protein kinase 1; mitogen activated protein kinase 3; stat3 transcription factor; bone marrow transplantation; graft vs host disease; t lymphocyte activation; allotransplantation; mitogen-activated protein kinase 3; 2 (2 amino 3 methoxyphenyl)chromone; alpha [amino(4 aminophenylthio)methylene] 2 (trifluoromethyl)phenylacetonitrile; cucurbitacin; cucurbitacin e; cucurbitacin i; stat3 protein, mouse
Journal Title: Blood
Volume: 112
Issue: 13
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2008-12-15
Start Page: 5254
End Page: 5258
Language: English
DOI: 10.1182/blood-2008-03-147322
PUBMED: 18838616
PROVIDER: scopus
PMCID: PMC2597618
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Christopher King
    29 King
  2. Sydney X Lu
    51 Lu
  3. Odette Marsinay Smith
    95 Smith
  4. David Suh
    41 Suh
  5. Adam Kochman
    45 Kochman
  6. Vanessa Marie Hubbard
    42 Hubbard
  7. Melanie Y Chow
    7 Chow
  8. Janine Chun Hsuen Lin
    4 Lin