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Cited by 39Protein Kinase Regulation and GTPase SignalingNF-κB Signaling PathwaysCellular transport and secretion

Regulation of RhoA GTPase and novel target proteins for ROCK

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Choi, Eun-Kyoung, Kim, Jae-Gyu, Kim, Hee-Jun, Cho, Jung-Yoon, Jeong, Hwalrim, Park, Yohan, Islam, Rokibul, Cap, Cuong Kim +1 more·2020·Small GTPases
DOI 10.1080/21541248.2017.1364831PMC PMC7053945
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Abstract

Rho GTPases play significant roles in cellular function and their activity is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), providing activation and inactivation of these GTPases, respectively. Active GTP-bound form of RhoA activates its effector proteins while the inactive GDP-bound form of RhoA exists in a RhoA-RhoGDI (guanine nucleotide dissociation inhibitor) complex in the cytosol. In particular, IκB kinase γ IKKγ/NF-κB essential modulator (NEMO) plays a role as a GDI displacement factor (GDF) for RhoA activation through binding to RhoA-RhoGDI complex. Meanwhile, prion protein inactivates RhoA despite RhoA/RhoGDI association. Novel target proteins for Rho-associated kinase (ROCK) such as glycogen synthase kinase (GSK)-3β and IKKβ are recently discovered. Here, we elaborate on a post-translationally modified version of RhoA, phosphorylated at Tyr42 and oxidized at Cys16/20. This form of RhoA dissociates from RhoA-RhoGDI complex and activates IKKβ on IKKγ/NEMO, thus providing possibly a critical role for tumourigenesis.

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  • Before a GTPase can be activated by GEFs, it needs to be dissociated from GDI because GEFs cannot directly act on the GTPase-GDI complex.

    “Before the GTPase can be activated by GEFs, it needs to be dissociated from the GDI as GEFs cannot directly act on the GTPase–GDI complex. This step is facilitated by GDI displacement factors (GDFs) (Figure 2A) [16].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [16]

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Research works printed but not linked: 44

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Cited by

Sorted by citations

Authors
Choi, E.-K., Kim, J.-G., Kim, H.-J., Cho, J.-Y., Jeong, H., Park, Y., Islam, R., Cap, C. K., & Park, J.-B.
Affiliations
Hallym University (KR)
Corresponding author
Park, Jae-Bong
ORCID
Venue
Small GTPases
Publisher
Informa UK Limited
Published
2017-12-03
Volume
11
Issue
2
Pages
95-102
ISSN
  • 2154-1248 (ISSN-L)
  • 2154-1256
DOI
10.1080/21541248.2017.1364831
PMC
PMC7053945
OpenAlex
W2772801538
Cited by
39
References
2
Citations by year
2026: 2 · 2025: 3 · 2024: 11 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 1
FWCI
0.18
Type
journal article
Language
en
Open access
Locations
  • Small GTPases (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation
  • Hallym University (HRF-S-52)
  • National Research Foundation of Korea
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
RhoA GTPase, Rho kinase, RhoGDI, guanine nucleotide exchange factor, GTPase-activating protein, NEMO, IKKγ, IKKβ, glycogen synthase kinase-3β, prion protein, post-translational modification, tumourigenesis, NF-κB signaling
MeSH terms
Animals, Humans, rhoA GTP-Binding Protein, rho-Associated Kinases

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