ArticleThe Journal of biological chemistry2015
The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1·Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1·Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- The Rho guanine-nucleotide exchange factor P-Rex2 exhibits structural and regulatory features distinct from the related RhoGEF P-Rex1.The Journal of biological chemistry · 2026Article
- P-Rex2 exhibits unique structural features and regulatory mechanisms distinct from the closely related RhoGEF P-Rex1.bioRxiv : the preprint server for biology · 2026Article
- P-Rex1 limits the agonist-induced internalization of GPCRs independently of its Rac-GEF activity.Cell reports · 2025Article
- P-Rex2 suppresses glucose uptake into liver and skeletal muscle through different adaptor functions.Scientific reports · 2025Article
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- Understanding P-Rex regulation: structural breakthroughs and emerging perspectives.Biochemical Society transactions · 2024Review
- New Mechanisms Underlying Oncogenesis in Dbl Family Rho Guanine Nucleotide Exchange Factors.Molecular pharmacology · 2024Review
- Article
- Structural and dynamic changes in P-Rex1 upon activation by PIPbioRxiv : the preprint server for biology · 2024Article
- Agent-based modeling predicts RAC1 is critical for ovarian cancer metastasis.Molecular biology of the cell · 2022Article
- Structure of the metastatic factor P-Rex1 reveals a two-layered autoinhibitory mechanism.Nature structural & molecular biology · 2022Article
- Small-molecule inhibitors of P-Rex guanine-nucleotide exchange factors.Small GTPases · 2022Article
- Mechanistic Differences of Activation of Rac1The journal of physical chemistry. B · 2021Article
- Review
- P-Rex1 Cooperates With TGFβR2 to Drive Lung Fibroblast Migration in Pulmonary Fibrosis.Frontiers in pharmacology · 2021Article
- GαThe Journal of biological chemistry · 2020Article
- The molecular basis for immune dysregulation by the hyperactivated E62K mutant of the GTPase RAC2.The Journal of biological chemistry · 2020Article
- Feedback regulation between phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 and transforming growth factor β1 and prognostic value in gastric cancer.World journal of gastroenterology · 2020Article
- Cryo-electron microscopy structure and analysis of the P-Rex1-Gβγ signaling scaffold.Science advances · 2019Article
- cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The P-Rex (phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of the Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion, and metastasis in several human cancers. The family is unique among Rho GEFs, as their activity is regulated by the synergistic binding of PIP3 and Gβγ at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 Å crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1·Rac1 interface revealed a critical role for this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. The structural data indicated that the PIP3/Gβγ binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gβγ releases inhibitory C-terminal domains to expose the Rac1 binding site.
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Registered trials
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.