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The interaction of Ras with GTPase‐activating proteins
Abstract
Ras plays a major role as a molecular switch in many signal transduction pathways which lead to cell growth and differentiation. The GTPase reaction of Ras is of central importance in the function of the switch since it terminates Ras‐effector interactions. GTPase‐activating proteins (GAPs) accelerate the very slow intrinsic hydrolysis reaction of the GTP‐bound Ras by several orders of magnitude and thereby act as presumably negative regulators of Ras action. The GTP hydrolysis of oncogenic mutants of Ras remains unaltered. In this review we discuss recent biochemical and structural findings relating to the mechanism of GAP action, which strengthen the hypothesis that GAP accelerates the actual cleavage step by stabilizing the transition state of the phosphoryl transfer reaction.
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“Activated RAS proteins can interact with many downstream effector proteins, such as RAF kinase, son of sevenless (SOS), phosphatidylinositol 3-kinase (PI3K) and Ral guanine nucleotide dissociation stimulating factors (RalGDS), which regulate cell events such as cell proliferation and apoptosis.323–325”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [324]
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Metadata
- Authors
- Wittinghofer, A., Scheffzek, K., & Ahmadian, M. R.
- Affiliations
- Max Planck Institute of Molecular Physiology (DE)
- Corresponding author
- Wittinghofer, Alfred
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1997-06-23
- Volume
- 410
- Issue
- 1
- Pages
- 63-67
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2001438210
- Cited by
- 135
- References
- 58
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 5 · 2017: 2 · 2016: 3 · 2015: 7 · 2014: 2 · 2013: 1 · 2012: 5
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Ras, GTPase-activating protein, GTP hydrolysis, signal transduction, transition state stabilization, phosphoryl transfer
- MeSH terms
- Animals, Humans, Models, Molecular, Protein Conformation, Proteins, ras Proteins, GTPase-Activating Proteins, ras GTPase-Activating Proteins
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