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Cited by 35T-cell and B-cell ImmunologyProtein Kinase Regulation and GTPase SignalingReceptor Mechanisms and Signaling

RhoH Regulates Subcellular Localization of ZAP-70 and Lck in T Cell Receptor Signaling

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Chae, Hee-Don, Siefring, Jamie E., Hildeman, David A., Gu, Yi, Williams, David A.·2010·PLoS ONE
DOI 10.1371/journal.pone.0013970PMC PMC2980477
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Abstract

RhoH is an hematopoietic-specific, GTPase-deficient Rho GTPase that plays a role in T development. We investigated the mechanisms of RhoH function in TCR signaling. We found that the association between Lck and CD3ζ was impaired in RhoH-deficient T cells, due to defective translocation of both Lck and ZAP-70 to the immunological synapse. RhoH with Lck and ZAP-70 localizes in the detergent-soluble membrane fraction where the complex is associated with CD3ζ phosphorylation. To determine if impaired translocation of ZAP-70 was a major determinant of defective T cell development, Rhoh(-/-) bone marrow cells were transduced with a chimeric myristoylation-tagged ZAP-70. Myr-ZAP-70 transduced cells partially reversed the in vivo defects of RhoH-associated thymic development and TCR signaling. Together, our results suggest that RhoH regulates TCR signaling via recruitment of ZAP-70 and Lck to CD3ζ in the immunological synapse. Thus, we define a new function for a RhoH GTPase as an adaptor molecule in TCR signaling pathway.

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  • Studies on RhoH-/- mice have observed a defect in thymocyte selection, maturation, lower T-cell cytotoxicity and cytokine release, and demonstrated that it is a result of reduced activation of ZAP70-mediated signaling and impaired translocation of ZAP70 to the immunological synapse.

    “Studies on RhoH -/-mice have observed a defect in thymocyte selection, maturation, lower T-cell cytotoxicity and cytokine release, and have demonstrated that it is a result of reduced activation of ZAP70-mediated signaling and impaired translocation of ZAP70 to the immunological synapse (5,9).”

    From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [9]

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Cited by

Sorted by citations

Authors
Chae, H.-D., Siefring, J. E., Hildeman, D. A., Gu, Y., & Williams, D. A.
Affiliations
Cincinnati Children's Hospital Medical Center (US)
Corresponding author
Williams, David A.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-11-12
Volume
5
Issue
11
Pages
e13970
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0013970
PMC
PMC2980477
OpenAlex
W1980354175
Cited by
35
References
0
Citations by year
2026: 1 · 2024: 5 · 2023: 2 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 6 · 2012: 4
FWCI
1.37
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Università degli Studi di Siena
  • King's College London
  • National Institutes of Health
  • University of California, San Francisco
  • National Cancer Institute (R01CA113969)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
RhoH, ZAP-70, Lck, T cell receptor signaling, immunological synapse, CD3, subcellular localization, thymus development, adaptor molecules, myristoylation, Rho GTPases, T cell development
MeSH terms
Animals, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Phosphorylation, Protein Binding, Receptors, Antigen, T-Cell, T-Lymphocytes, Transcription Factors, Immunoblotting, Signal Transduction, CD3 Complex, Mice, Knockout, Jurkat Cells, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), rho GTP-Binding Proteins, Intracellular Space, Mice, ZAP-70 Protein-Tyrosine Kinase, Mice, 129 Strain, HEK293 Cells

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