ArticleBiochemistry2008
Role of the C-terminal SH3 domain and N-terminal tyrosine phosphorylation in regulation of Tim and related Dbl-family proteins.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Activity-dependent regulation of Cdc42 by Ephexin5 drives synapse growth and stabilization.Science advances · 2025Article
- Phosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division.The Journal of biological chemistry · 2025Article
- New Mechanisms Underlying Oncogenesis in Dbl Family Rho Guanine Nucleotide Exchange Factors.Molecular pharmacology · 2024Review
- Solo regulates the localization and activity of PDZ-RhoGEF for actin cytoskeletal remodeling in response to substrate stiffness.Molecular biology of the cell · 2024Article
- Dishevelled2 activates WGEF via its interaction with a unique internal peptide motif of the GEF.Communications biology · 2024Article
- FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma.Cell reports · 2021Article
- Akt-mediated Ephexin1-Ras interaction promotes oncogenic Ras signaling and colorectal and lung cancer cell proliferation.Cell death & disease · 2021Article
- The Integrin Signaling Network Promotes Axon Regeneration via the Src-Ephexin-RhoA GTPase Signaling Axis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Double inhibition and activation mechanisms of Ephexin family RhoGEFs.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Multiplexed GTPase and GEF biosensor imaging enables network connectivity analysis.Nature chemical biology · 2020Article
- Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.Molecules (Basel, Switzerland) · 2019Review
- Review
- Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1.Scientific reports · 2017Article
- Mutation of Vav1 adaptor region reveals a new oncogenic activation.Oncotarget · 2015Article
- Intramolecular interactions between the Dbl homology (DH) domain and the carboxyl-terminal region of myosin II-interacting guanine nucleotide exchange factor (MyoGEF) act as an autoinhibitory mechanism for the regulation of MyoGEF functions.The Journal of biological chemistry · 2014Article
- Tyrosine phosphorylation of Dbl regulates GTPase signaling.The Journal of biological chemistry · 2014Article
- PLEKHG2 promotes heterotrimeric G protein βγ-stimulated lymphocyte migration via Rac and Cdc42 activation and actin polymerization.Molecular and cellular biology · 2013Article
- Structural basis for autoinhibition of the guanine nucleotide exchange factor FARP2.Structure (London, England : 1993) · 2013Article
- Rho GTPases in primary brain tumor malignancy and invasion.Journal of neuro-oncology · 2012Review
- Essential role of the NH2-terminal region of Cdc24 guanine nucleotide exchange factor in its initial polarized localization in Saccharomyces cerevisiae.Eukaryotic cell · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Dbl-related oncoproteins are guanine nucleotide exchange factors (GEFs) specific for Rho-family GTPases and typically possess tandem Dbl (DH) and pleckstrin homology (PH) domains that act in concert to catalyze exchange. Although the exchange potential of many Dbl-family proteins is constitutively activated by truncation, the precise mechanisms of regulation for many Dbl-family proteins are unknown. Tim and Vav are distantly related Dbl-family proteins that are similarly regulated; their Dbl homology (DH) domains interact with N-terminal helices to exclude and prevent activation of Rho GTPases. Phosphorylation, substitution, or deletion of the blocking helices relieves this autoinhibition. Here we show that two other Dbl-family proteins, Ngef and Wgef, which like Tim contain a C-terminal SH3 domain, are also activated by tyrosine phosphorylation of a blocking helix. Consequently, basal autoinhibition of DH domains by direct steric exclusion using short N-terminal helices likely represents a conserved mechanism of regulation for the large family of Dbl-related proteins. N-Terminal truncation or phosphorylation of many other Dbl-family GEFs leads to their activation; similar autoinhibition mechanisms could explain some of these events. In addition, we show that the C-terminal SH3 domain binding to a polyproline region N-terminal to the DH domain of the Tim subgroup of Dbl-family proteins provides a unique mechanism of regulated autoinhibition of exchange activity that is functionally linked to the interactions between the autoinhibitory helix and the DH domain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.