ArticleThe Biochemical journal2004
Inositol phospholipids regulate the guanine-nucleotide-exchange factor Tiam1 by facilitating its binding to the plasma membrane and regulating GDP/GTP exchange on Rac1.
Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 49 citations in OpenAlex.
- Protective Effect of myo-Inositol Against Decitabine-Induced Neural Tube Defects in Embryonic Zebrafish.Neurotoxicity research · 2025Article
- The Role of FNDC4 in Inflammation and Metabolism for Various Diseases.Aging and disease · 2024Review
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- Myo-Inositol as a Key Supporter of Fertility and Physiological Gestation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Pleiotropic Roles of Calmodulin in the Regulation of KRas and Rac1 GTPases: Functional Diversity in Health and Disease.International journal of molecular sciences · 2020Review
- ADP-ribosylation factor 6 (ARF6) bidirectionally regulates dendritic spine formation depending on neuronal maturation and activity.The Journal of biological chemistry · 2015Article
- Rapid dispersion of SynGAP from synaptic spines triggers AMPA receptor insertion and spine enlargement during LTP.Neuron · 2015Article
- Crossroads of PI3K and Rac pathways.Small GTPases · 2015Review
- High-resolution structure of the Tiam1 PHn-CC-Ex domain.Acta crystallographica. Section F, Structural biology and crystallization communications · 2013Article
- Article
- Signaling via class IA Phosphoinositide 3-kinases (PI3K) in human, breast-derived cell lines.PloS one · 2013Article
- Tiam1 is recruited to β1-integrin complexes by 14-3-3ζ where it mediates integrin-induced Rac1 activation and motility.Journal of cellular physiology · 2011Article
- Scaffold proteins IRSp53 and spinophilin regulate localized Rac activation by T-lymphocyte invasion and metastasis protein 1 (TIAM1).The Journal of biological chemistry · 2010Article
- Tiam1 and Rac1 are required for platelet-activating factor-induced endothelial junctional disassembly and increase in vascular permeability.The Journal of biological chemistry · 2009Article
- Regulatory roles for Tiam1, a guanine nucleotide exchange factor for Rac1, in glucose-stimulated insulin secretion in pancreatic beta-cells.Biochemical pharmacology · 2009Article
- SynGAP regulates steady-state and activity-dependent phosphorylation of cofilin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
- The guanine nucleotide exchange factors trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma.The American journal of pathology · 2008Article
- Molecular responses of the Ts65Dn and Ts1Cje mouse models of Down syndrome to MK-801.Genes, brain, and behavior · 2008Article
- Neurotrophin-dependent dendritic filopodial motility: a convergence on PI3K signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
- Essential role for Rac in heregulin beta1 mitogenic signaling: a mechanism that involves epidermal growth factor receptor and is independent of ErbB4.Molecular and cellular biology · 2006Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Binding of the Rac1-specific guanine-nucleotide-exchange factor, Tiam1, to the plasma membrane requires the N-terminal pleckstrin homology domain. In the present study, we show that membrane-association is mediated by binding of PtdIns(4,5)P(2) to the pleckstrin homology domain. Moreover, in 1321N1 astrocytoma cells, translocation of Tiam1 to the cytosol, following receptor-mediated stimulation of PtdIns(4,5)P(2) breakdown, correlates with decreased Rac1-GTP levels, indicating that membrane-association is required for GDP/GTP exchange on Rac1. In addition, we show that platelet-derived growth factor activates Rac1 in vivo by increasing PtdIns(3,4,5)P(3) concentrations, rather than the closely related lipid, PtdIns(3,4)P(2). Finally, the data demonstrate that PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3) bind to the same pleckstrin homology domain in Tiam1 and that soluble inositol phosphates appear to compete with lipids for this binding. Together, these novel observations provide strong evidence that distinct phosphoinositides regulate different functions of this enzyme, indicating that local concentrations of signalling lipids and the levels of cytosolic inositol phosphates will play crucial roles in determining its activity in vivo.
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