Cited by 135Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesCellular transport and secretion

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The interaction of Ras with GTPase‐activating proteins

Wittinghofer, Alfred, Scheffzek, Klaus, Ahmadian, Mohammad Reza·1997·FEBS Letters

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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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Authors: Wittinghofer, A., Scheffzek, K., & Ahmadian, M. R.
Affiliations: Max Planck Institute of Molecular Physiology (DE)
Corresponding author: Wittinghofer, Alfred
ORCID: Wittinghofer, Alfred
Scheffzek, Klaus
Ahmadian, Mohammad Reza
Venue: FEBS Letters
Publisher: Wiley
Published: 1997-06-23
Volume: 410
Issue: 1
Pages: 63-67
ISSN: 0014-5793 (ISSN-L)
1873-3468
DOI: 10.1016/s0014-5793(97)00321-9
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 232 d)
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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The interaction of Ras with GTPase‐activating proteins

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