ArticleThe Journal of biological chemistry2016
IQGAP1 Interaction with RHO Family Proteins Revisited: KINETIC AND EQUILIBRIUM EVIDENCE FOR MULTIPLE DISTINCT BINDING SITES.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- IqgD is a Rac1-interacting IQGAP required for efficient growth of Dictyostelium discoideum on bacterial lawns.Cell communication and signaling : CCS · 2026Article
- IQGAP Family Proteins in Colorectal Cancer: Molecular Mechanisms and Prognostic Implications.Diagnostics (Basel, Switzerland) · 2026Review
- Queue Gaps Among the IQGAPs inInternational journal of molecular sciences · 2026Review
- Actin dynamics controlled by IqgC, a RasGAP at the crossroads between the IQGAP and fungal GAP1 families.FEBS open bio · 2026Review
- New insights into the classification of the RAC1 P29S hotspot mutation in melanoma as an oncogene.Cancer gene therapy · 2025Article
- The IQGAP-related RasGAP IqgC regulates cell-substratum adhesion in Dictyostelium discoideum.Cellular & molecular biology letters · 2025Article
- Article
- Haldol Targets IQGAP1 Pathway and Promotes Novel Partner Interactions in Glioblastoma Cell Lines.microPublication biology · 2023Article
- CDC42-IQGAP Interactions Scrutinized: New Insights into the Binding Properties of the GAP-Related Domain.International journal of molecular sciences · 2022Article
- Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma.Frontiers in oncology · 2022Review
- Selectivity Determinants of RHO GTPase Binding to IQGAPs.International journal of molecular sciences · 2021Article
- RAC1 Activation as a Potential Therapeutic Option in Metastatic Cutaneous Melanoma.Biomolecules · 2021Review
- Macrothrombocytopenia of Takenouchi-Kosaki syndrome is ameliorated by CDC42 specific- and lipidation inhibitors in MEG-01 cells.Scientific reports · 2021Article
- Pleiotropic Roles of Calmodulin in the Regulation of KRas and Rac1 GTPases: Functional Diversity in Health and Disease.International journal of molecular sciences · 2020Review
- Ubiquitination of the scaffold protein IQGAP1 diminishes its interaction with and activation of the Rho GTPase CDC42.The Journal of biological chemistry · 2020Article
- Membrane and Actin Tethering Transitions Help IQGAP1 Coordinate GTPase and Lipid Messenger Signaling.Biophysical journal · 2020Article
- New model for the interaction of IQGAP1 with CDC42 and RAC1.Small GTPases · 2020Review
- A kinome-wide screen using a NanoLuc LATS luminescent biosensor identifies ALK as a novel regulator of the Hippo pathway in tumorigenesis and immune evasion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Identification of Celastrol as a Novel YAP-TEAD Inhibitor for Cancer Therapy by High Throughput Screening with UltrasensitiveCancers · 2019Article
- Site-specific expression of IQGAP1 in human nephrons.Journal of molecular histology · 2019Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
IQ motif-containing GTPase activating protein 1 (IQGAP1) plays a central role in the physical assembly of relevant signaling networks that are responsible for various cellular processes, including cell adhesion, polarity, and transmigration. The RHO family proteins CDC42 and RAC1 have been shown to mainly interact with the GAP-related domain (GRD) of IQGAP1. However, the role of its RASGAP C-terminal (RGCT) and C-terminal domains in the interactions with RHO proteins has remained obscure. Here, we demonstrate that IQGAP1 interactions with RHO proteins underlie a multiple-step binding mechanism: (i) a high affinity, GTP-dependent binding of RGCT to the switch regions of CDC42 or RAC1 and (ii) a very low affinity binding of GRD and a C terminus adjacent to the switch regions. These data were confirmed by phosphomimetic mutation of serine 1443 to glutamate within RGCT, which led to a significant reduction of IQGAP1 affinity for CDC42 and RAC1, clearly disclosing the critical role of RGCT for these interactions. Unlike CDC42, an extremely low affinity was determined for the RAC1-GRD interaction, suggesting that the molecular nature of IQGAP1 interaction with CDC42 partially differs from that of RAC1. Our study provides new insights into the interaction characteristics of IQGAP1 with RHO family proteins and highlights the complementary importance of kinetic and equilibrium analyses. We propose that the ability of IQGAP1 to interact with RHO proteins is based on a multiple-step binding process, which is a prerequisite for the dynamic functions of IQGAP1 as a scaffolding protein and a critical mechanism in temporal regulation and integration of IQGAP1-mediated cellular responses.
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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.