ArticleThe Journal of biological chemistry2008
rac regulates its effector phospholipase Cgamma2 through interaction with a split pleckstrin homology domain.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- PLCG2 exon-skipped variants: insights into their potential role in chronic lymphocytic leukemia.Blood advances · 2026Article
- A phosphatidylinositol phosphate kinase inhibits Ras activation and regulates chemorepulsion in Dictyostelium discoideum.Journal of cell science · 2023Article
- Activation Mechanisms and Diverse Functions of Mammalian Phospholipase C.Biomolecules · 2023Review
- Not too little, not too much: the impact of mutation types in Wiskott-Aldrich syndrome and RAC2 patients.Clinical and experimental immunology · 2023Review
- Variant in theJournal of clinical medicine · 2022Article
- Dynamics of allosteric regulation of the phospholipase C-γ isozymes upon recruitment to membranes.eLife · 2022Article
- Noncatalytic Bruton's tyrosine kinase activates PLCγThe Journal of biological chemistry · 2020Article
- Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations.eLife · 2019Article
- K-Ras G-domain binding with signaling lipid phosphatidylinositol (4,5)-phosphate (PIP2): membrane association, protein orientation, and function.The Journal of biological chemistry · 2019Article
- Functional characterization of phospholipase C-γOncotarget · 2018Article
- Dynamic Allostery in PLCγ1 and Its Modulation by a Cancer Mutation Revealed by MD Simulation and NMR.Biophysical journal · 2018Article
- The Phospholipase Cγ2 Mutants R665W and L845F Identified in Ibrutinib-resistant Chronic Lymphocytic Leukemia Patients Are Hypersensitive to the Rho GTPase Rac2 Protein.The Journal of biological chemistry · 2016Article
- Rac-mediated Stimulation of Phospholipase Cγ2 Amplifies B Cell Receptor-induced Calcium Signaling.The Journal of biological chemistry · 2015Article
- Mechanism of Rac1-induced amplification in gastric mucosal phospholipase Cγ2 activation in response to Helicobacter pylori: modulatory effect of ghrelin.Inflammopharmacology · 2015Article
- Regulatory role of guanine nucleotide exchange factor (GEF) Dock180 phosphorylation on Tyr/Ser in mediation of gastric mucosal Rac1 activation in response to Helicobacter pylori and ghrelin.Inflammopharmacology · 2015Article
- Lipid and Protein Co-Regulation of PI3K Effectors Akt and Itk in Lymphocytes.Frontiers in immunology · 2015Review
- Competition between Grb2 and Plcγ1 for FGFR2 regulates basal phospholipase activity and invasion.Nature structural & molecular biology · 2014Article
- The Concise Guide to PHARMACOLOGY 2013/14: enzymes.British journal of pharmacology · 2013Article
- Phosphoinositides: tiny lipids with giant impact on cell regulation.Physiological reviews · 2013Review
- The phospholipase C isozymes and their regulation.Sub-cellular biochemistry · 2012Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Several isoforms of phospholipase C (PLC) are regulated through interactions with Ras superfamily GTPases, including Rac proteins. Interestingly, of two closely related PLCgamma isoforms, only PLCgamma(2) has previously been shown to be activated by Rac. Here, we explore the molecular basis of this interaction as well as the structural properties of PLCgamma(2) required for activation. Based on reconstitution experiments with isolated PLCgamma variants and Rac2, we show that an unusual pleckstrin homology (PH) domain, designated as the split PH domain (spPH), is both necessary and sufficient to effect activation of PLCgamma(2) by Rac2. We also demonstrate that Rac2 directly binds to PLCgamma(2) as well as to the isolated spPH of this isoform. Furthermore, through the use of NMR spectroscopy and mutational analysis, we determine the structure of spPH, define the structural features of spPH required for Rac interaction, and identify critical amino acid residues at the interaction interface. We further discuss parallels and differences between PLCgamma(1) and PLCgamma(2) and the implications of our findings for their respective signaling roles.
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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.