ArticleMolecular biology of the cell2002
Localization of phospholipase D1 to caveolin-enriched membrane via palmitoylation: implications for epidermal growth factor signaling.
Article in Molecular biology of the cell, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Disruption of palmitate-mediated localization; a shared pathway of force and anesthetic activation of TREK-1 channels.Biochimica et biophysica acta. Biomembranes · 2020Review
- Phospholipase D2 in prostate cancer: protein expression changes with Gleason score.British journal of cancer · 2019Article
- Pharmacological and Genetic Inhibition of Caveolin-1 Promotes Epithelialization and Wound Closure.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies.Chemical reviews · 2018Article
- Inhibition ofJournal of Cancer · 2018Article
- Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in prion disease.PloS one · 2015Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Disulphide bridges of phospholipase C of Chlamydomonas reinhardtii modulates lipid interaction and dimer stability.PloS one · 2012Article
- 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
- Protein kinase C: the "masters" of calcium and lipid.Cold Spring Harbor perspectives in biology · 2011Review
- Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced apoptosis.Free radical biology & medicine · 2011Article
- Caveolin-1: a critical regulator of lung injury.American journal of physiology. Lung cellular and molecular physiology · 2011Review
- Protein kinase Cdelta-mediated phosphorylation of phospholipase D controls integrin-mediated cell spreading.Molecular and cellular biology · 2010Article
- New concepts in phospholipase D signaling in inflammation and cancer.TheScientificWorldJournal · 2010Review
- A comprehensive model that explains the regulation of phospholipase D2 activity by phosphorylation-dephosphorylation.Molecular and cellular biology · 2010Article
- 12-O-tetradecanoylphorbol-13-acetate inhibits melanoma growth by inactivation of STAT3 through protein kinase C-activated tyrosine phosphatase(s).The Journal of biological chemistry · 2009Article
- Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.PloS one · 2009Article
- Phospholipase D in the Golgi apparatus.Biochimica et biophysica acta · 2009Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phospholipase D (PLD) has been suggested to mediate epidermal growth factor (EGF) signaling. However, the molecular mechanism of EGF-induced PLD activation has not yet been elucidated. We investigated the importance of the phosphorylation and compartmentalization of PLD1 in EGF signaling. EGF treatment of COS-7 cells transiently expressing PLD1 stimulated PLD1 activity and induced PLD1 phosphorylation. The EGF-induced phosphorylation of threonine147 was completely blocked and the activity of PLD1 attenuated by point mutations (S2A/T147A/S561A) of PLD1 phosphorylation sites. The expression of a dominant negative PKCalpha mutant by adenovirus-mediated gene transfer greatly inhibited the phosphorylation and activation of PLD1 induced by EGF in PLD1-transfected COS-7 cells. EGF-induced PLD1 phosphorylation occurred primarily in the caveolin-enriched membrane (CEM) fraction, and the kinetics of PLD1 phosphorylation in the CEM were strongly correlated with PLD1 phosphorylation in the total membrane. Interestingly, EGF-induced PLD1 phosphorylation and activation and the coimmunoprecipitation of PLD1 with caveolin-1 and the EGF receptor in the CEM were significantly attenuated in the palmitoylation-deficient C240S/C241S mutant, which did not localize to the CEM. Immunocytochemical analysis revealed that wild-type PLD1 colocalized with caveolin-1 and the EGF receptor and that phosphorylated PLD1 was localized exclusively in the plasma membrane, although some PLD1 was also detected in vesicular structures. Transfection of wild-type PLD1 but not of C240S/C241S mutant increased EGF-induced raf-1 translocation to the CEM and ERK phosphorylation. This study shows, for the first time, that EGF-induced PLD1 phosphorylation and activation occur in the CEM and that the correct localization of PLD1 to the CEM via palmitoylation is critical for EGF signaling.
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