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Cited by 25Protein Kinase Regulation and GTPase SignalingT-cell and B-cell ImmunologyCellular transport and secretion

The Role of RhoH in TCR Signalling and Its Involvement in Diseases

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Ahmad Mokhtar, Ana Masara, Hashim, Ilie Fadzilah, Mohd Zaini Makhtar, Muaz, Salikin, Nor Hawani, Amin-Nordin, Syafinaz·2021·Cells
DOI 10.3390/cells10040950PMC PMC8072805
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Abstract

As an atypical member of the Rho family small GTPases, RhoH shares less than 50% sequence similarity with other members, and its expression is commonly observed in the haematopoietic lineage. To date, RhoH function was observed in regulating T cell receptor signalling, and less is known in other haematopoietic cells. Its activation may not rely on the standard GDP/GTP cycling of small G proteins and is thought to be constitutively active because critical amino acids involved in GTP hydrolysis are absent. Alternatively, its activation can be regulated by other types of regulation, including lysosomal degradation, somatic mutation and transcriptional repressor, which also results in an altered protein expression. Aberrant protein expression of RhoH has been implicated not only in B cell malignancies but also in immune-related diseases, such as primary immunodeficiencies, systemic lupus erythematosus and psoriasis, wherein its involvement may provide the link between immune-related diseases and cancer. RhoH association with these diseases involves several other players, including its interacting partner, ZAP−70; activation regulators, Vav1 and RhoGDI and other small GTPases, such as RhoA, Rac1 and Cdc42. As such, RhoH and its associated proteins are potential attack points, especially in the treatment of cancer and immune-related diseases.

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  • RHOH exerts a critical role in the activation, development and differentiation of T lymphocytes.

    “As a membrane-bound adaptor for proximal protein kinases involved in TCR signal transduction, RHOH exerts a critical role in the activation, development and differentiation of T lymphocytes (1,4).”

    From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [4]

    Section 2 describes RhoH as an adaptor that recruits kinases for TCR signalling and calls that signalling crucial for T-cell activation and development; it also describes RhoH’s membrane targeting. Section 3.2.2 links loss of RhoH to increased differentiation into TH17 cells, but says development of some unconventional T-cell subsets is not critically dependent on RhoH-mediated signalling. The source therefore supports a role in differentiation, not an unqualified critical role across T lymphocytes. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Disruption of RHOH gene has been associated with various types of B-cell malignancies and inborn errors of immunity.

    “Disruption of RHOH (MIM: 602037) gene has been associated with various types of B-cell malignancies (4) and inborn errors of immunity (IEI) (6).”

    From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [4]

  • RHOH is involved in T-cell receptor signaling through the recruitment and activation of ZAP70 and LCK.

    “RHOH is involved in T-cell receptor signaling through the recruitment and activation of ZAP70 and LCK (4,5).”

    From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [4]

  • Somatic mutations in RHOH gene have been linked to certain hematological malignancies.

    “Somatic mutations in RHOH gene have been linked to certain hematological malignancies (4).”

    From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [4]

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Cited by

Sorted by citations

Authors
Ahmad Mokhtar, A. M., Hashim, I. F., Mohd Zaini Makhtar, M., Salikin, N. H., & Amin-Nordin, S.
Affiliations
  • Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia
  • Universiti Sains Malaysia (MY)
  • Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-04-20
Volume
10
Issue
4
Pages
950
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells10040950
PMC
PMC8072805
OpenAlex
W3156127592
Cited by
25
References
2
Citations by year
2026: 3 · 2025: 3 · 2024: 9 · 2023: 3 · 2022: 3 · 2021: 4
FWCI
0.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Universiti Putra Malaysia Institutional Repository (Universiti Putra Malaysia) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
RhoH, Rho GTPases, T cell receptor signaling, hematopoietic cells, B-cell malignancies, primary immunodeficiency, systemic lupus erythematosus, psoriasis, ZAP-70, Vav1, RhoGDI, RhoA, Rac1, Cdc42, therapeutic target
MeSH terms
Amino Acid Sequence, Animals, Disease, Humans, Models, Biological, Receptors, Antigen, T-Cell, Signal Transduction, rho GTP-Binding Proteins, Molecular Targeted Therapy

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