ArticleJournal of molecular biology2007
The Grb2/PLD2 interaction is essential for lipase activity, intracellular localization and signaling in response to EGF.
Article in Journal of molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
- Structure and regulation of human phospholipase D.Advances in biological regulation · 2021Review
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Regulation of Membrane Turnover by Phosphatidic Acid: Cellular Functions and Disease Implications.Frontiers in cell and developmental biology · 2019Review
- The Lipase Activity of Phospholipase D2 is Responsible for Nigral Neurodegeneration in a Rat Model of Parkinson's Disease.Neuroscience · 2018Article
- Phosphatidic Acid (PA) can Displace PPARα/LXRα Binding to The EGFR Promoter Causing its Transrepression in Luminal Cancer Cells.Scientific reports · 2015Article
- Phosphatidic Acid Increases Epidermal Growth Factor Receptor Expression by Stabilizing mRNA Decay and by Inhibiting Lysosomal and Proteasomal Degradation of the Internalized Receptor.Molecular and cellular biology · 2015Article
- Impact of Hybrid and Complex N-Glycans on Cell Surface Targeting of the Endogenous Chloride Cotransporter Slc12a2.International journal of cell biology · 2015Article
- Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis.The Journal of biological chemistry · 2014Review
- Identification of the catalytic site of phospholipase D2 (PLD2) newly described guanine nucleotide exchange factor activity.The Journal of biological chemistry · 2012Article
- Biochemical and cellular implications of a dual lipase-GEF function of phospholipase D2 (PLD2).Journal of leukocyte biology · 2012Review
- The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF).Cellular signalling · 2011Review
- A novel phospholipase D2-Grb2-WASp heterotrimer regulates leukocyte phagocytosis in a two-step mechanism.Molecular and cellular biology · 2011Article
- Phospholipase D: enzymology, functionality, and chemical modulation.Chemical reviews · 2011Review
- α-Synuclein expression in rat substantia nigra suppresses phospholipase D2 toxicity and nigral neurodegeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- The molecular basis of phospholipase D2-induced chemotaxis: elucidation of differential pathways in macrophages and fibroblasts.Molecular and cellular biology · 2010Article
- New concepts in phospholipase D signaling in inflammation and cancer.TheScientificWorldJournal · 2010Review
- Phosphatidic acid is a leukocyte chemoattractant that acts through S6 kinase signaling.The Journal of biological chemistry · 2010Article
- A comprehensive model that explains the regulation of phospholipase D2 activity by phosphorylation-dephosphorylation.Molecular and cellular biology · 2010Article
- The inhibition of tube formation in a collagen-fibrinogen, three-dimensional gel by cleaved kininogen (HKa) and HK domain 5 (D5) is dependent on Src family kinases.Experimental cell research · 2008Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The adaptor protein Grb2 associates with phospholipase D2 (PLD2), but it is not known if this interaction is necessary for the functionality of the lipase in vivo. We demonstrate that stable short hairpin RNA (shRNA)-based silencing of Grb2, a critical signal transducer of the epidermal growth factor receptor (EGFR) and linker to the Ras/Erk pathway, resulted in the reduction of PLD2 activity in COS7 cells. Transfection of a Grb2 construct refractory to shGrb2 silencing (XGrb2(SiL)) into the Grb2-knockdown cells (COS7(shGrb2)), resulted in the nearly full rescue of PLD2 activity. However, Grb2-R86K, an SH2-deficient mutant of Grb2 that is incapable of binding to PLD2, failed to induce an enhancement of the impaired PLD2 activity in COS7(shGrb2) cells. Grb2 and PLD2 are directly associated and Grb2 is brought down with anti-myc antibodies irrespective of the presence or absence of EGFR activation. Immunofluorescence microscopy showed that co-transfected PLD2 and Grb2 re-localize to Golgi-like structures after EGF stimulation. Since this was not observed in cotransfection experiments with Grb2 and PLD2-Y169/179F, a lipase mutant that does not bind to Grb2, we inferred that Grb2 serves to hijack PLD2 to the perinuclear Golgi region through its SH2 domain. Supporting this is the finding that the primary cell line HUVEC expresses PLD2 diffusely in the cytoplasm and in the perinuclear Golgi region, where PLD2 and Grb2 colocalize. Such colocalization in primary cells increased after stimulation with EGF. These results demonstrate for the first time that the presence of Grb2 and its interaction with localized intracellular structures is essential for PLD2 activity and signaling in vivo.
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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.