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Cited by 78Protein Kinase Regulation and GTPase SignalingCellular transport and secretionCellular Mechanics and Interactions

RLIP76 (RalBP1) is an R-Ras effector that mediates adhesion-dependent Rac activation and cell migration

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Goldfinger, Lawrence E., Ptak, Celeste, Jeffery, Erin D., Shabanowitz, Jeffrey, Hunt, Donald F., Ginsberg, Mark H.·2006·The Journal of Cell Biology
DOI 10.1083/jcb.200603111PMC PMC2064341
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Abstract

The Ras family of small GTPases regulates cell proliferation, spreading, migration and apoptosis, and malignant transformation by binding to several protein effectors. One such GTPase, R-Ras, plays distinct roles in each of these processes, but to date, identified R-Ras effectors were shared with other Ras family members (e.g., H-Ras). We utilized a new database of Ras-interacting proteins to identify RLIP76 (RalBP1) as a novel R-Ras effector. RLIP76 binds directly to R-Ras in a GTP-dependent manner, but does not physically associate with the closely related paralogues H-Ras and Rap1A. RLIP76 is required for adhesion-induced Rac activation and the resulting cell spreading and migration, as well as for the ability of R-Ras to enhance these functions. RLIP76 regulates Rac activity through the adhesion-induced activation of Arf6 GTPase and activation of Arf6 bypasses the requirement for RLIP76 in Rac activation and cell spreading. Thus, we identify a novel R-Ras effector, RLIP76, which links R-Ras to adhesion-induced Rac activation through a GTPase cascade that mediates cell spreading and migration.

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  • GTPase activating domain of Rlip is important for regulating Rac, Rho, and Cdc42.

    “The GTPase activating domain of Rlip is important for regulating Rac, Rho, and Cdc42 [103,104], downstream G-protein effectors of Rlip which are also master regulators of cytoskeletal remodeling and coordinate the movement of the cytoskeleton with consequent effects on organelles, vesicles, and the plasma membrane structures such as invadopodia [26,105,106].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [103]

    The Discussion says RLIP76’s RhoGAP domain is important for adhesion-dependent Rac activation and reports that it acts as a Rac and Cdc42 GAP in vitro. The passages do not establish that it regulates Rho; “RhoGAP” is the domain’s name, not evidence of that additional target. The Discussion also distinguishes the domain’s role in Rac activation from its GAP catalytic activity, which was not required for the observed effect in vivo. (LLM, conf=0.88)

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Cited by

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Authors
Goldfinger, L. E., Ptak, C., Jeffery, E. D., Shabanowitz, J., Hunt, D. F., & Ginsberg, M. H.
Affiliations
  • University of California San Diego (US)
  • 3Department of Chemistry and
  • University of Virginia (US)
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2006-09-11
Volume
174
Issue
6
Pages
877-888
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200603111
PMC
PMC2064341
OpenAlex
W2122437448
Cited by
78
References
0
Citations by year
2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 11
FWCI
1.76
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
Funders
  • National Institutes of Health (5u54gm064346-10)
  • National Heart, Lung, and Blood Institute (HL 57900, HL 078784, P01HL078784, P01HL057900)
  • National Institute of General Medical Sciences (U54-GM064346, GM37537, R01GM037537)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
RLIP76, RALBP1, R-Ras, Ras effectors, Rac activation, cell adhesion, cell migration, cell spreading, ARF6, H-Ras, Rap1A
MeSH terms
ADP-Ribosylation Factor 6, Animals, Cell Adhesion, Cell Movement, Fibroblasts, Guanosine Triphosphate, Protein Binding, Signal Transduction, ras Proteins, GTP Phosphohydrolases, GTPase-Activating Proteins, ADP-Ribosylation Factors, rac GTP-Binding Proteins, NIH 3T3 Cells, Cell Size, Mice

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