ArticleMolecular biology of the cell2011
Sequestration of phosphoinositides by mutated MARCKS effector domain inhibits stimulated Ca(2+) mobilization and degranulation in mast cells.
Article in Molecular biology of the cell, 2011. 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, 35 citations in OpenAlex.
- A molecular systems perspective on calcium oscillations beyond ion fluxes.Current opinion in cell biology · 2025Review
- Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function.Toxicology and applied pharmacology · 2022Article
- Measurement of Exocytosis in Genetically Manipulated Mast Cells.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Membrane Binding of Neuronal Calcium Sensor-1: Highly Specific Interaction with Phosphatidylinositol-3-Phosphate.Biomolecules · 2020Article
- Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition.Journal of applied toxicology : JAT · 2019Article
- Mal protein stabilizes luminal membrane PLC-β3 and negatively regulates ENaC in mouse cortical collecting duct cells.American journal of physiology. Renal physiology · 2019Article
- The long noncoding RNAThe EMBO journal · 2019Article
- Article
- MARCKS and Lung Disease.American journal of respiratory cell and molecular biology · 2019Review
- A PKC-MARCKS-PI3K regulatory module links Ca2+ and PIP3 signals at the leading edge of polarized macrophages.PloS one · 2018Article
- Prognostic value of a 25-gene assay in patients with gastric cancer after curative resection.Scientific reports · 2017Article
- Frontline Science: Tumor necrosis factor-α stimulation and priming of human neutrophil granule exocytosis.Journal of leukocyte biology · 2017Article
- Exocytosis of polyubiquitinated proteins in bortezomib-resistant leukemia cells: a role for MARCKS in acquired resistance to proteasome inhibitors.Oncotarget · 2016Article
- Roles for lipid heterogeneity in immunoreceptor signaling.Biochimica et biophysica acta · 2016Review
- Phosphatidylinositol phosphate kinase PIPKIγ and phosphatase INPP5E coordinate initiation of ciliogenesis.Nature communications · 2016Article
- Nanodomains in early and later phases of FcɛRI signalling.Essays in biochemistry · 2015Article
- In Vitro Neutrophil Migration Requires Protein Kinase C-Delta (δ-PKC)-Mediated Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Phosphorylation.Inflammation · 2015Article
- Distinct stages of stimulated FcεRI receptor clustering and immobilization are identified through superresolution imaging.Biophysical journal · 2013Article
- Multiple roles for the actin cytoskeleton during regulated exocytosis.Cellular and molecular life sciences : CMLS · 2013Review
- Protein kinase C pharmacology: refining the toolbox.The Biochemical journal · 2013Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase C β (PKCβ) participates in antigen-stimulated mast cell degranulation mediated by the high-affinity receptor for immunoglobulin E, FcεRI, but the molecular basis is unclear. We investigated the hypothesis that the polybasic effector domain (ED) of the abundant intracellular substrate for protein kinase C known as myristoylated alanine-rich protein kinase C substrate (MARCKS) sequesters phosphoinositides at the inner leaflet of the plasma membrane until MARCKS dissociates after phosphorylation by activated PKC. Real-time fluorescence imaging confirms synchronization between stimulated oscillations of intracellular Ca(2+) concentrations and oscillatory association of PKCβ-enhanced green fluorescent protein with the plasma membrane. Similarly, MARCKS-ED tagged with monomeric red fluorescent protein undergoes antigen-stimulated oscillatory dissociation and rebinding to the plasma membrane with a time course that is synchronized with reversible plasma membrane association of PKCβ. We find that MARCKS-ED dissociation is prevented by mutation of four serine residues that are potential sites of phosphorylation by PKC. Cells expressing this mutated MARCKS-ED SA4 show delayed onset of antigen-stimulated Ca(2+) mobilization and substantial inhibition of granule exocytosis. Stimulation of degranulation by thapsigargin, which bypasses inositol 1,4,5-trisphosphate production, is also substantially reduced in the presence of MARCKS-ED SA4, but store-operated Ca(2+) entry is not inhibited. These results show the capacity of MARCKS-ED to regulate granule exocytosis in a PKC-dependent manner, consistent with regulated sequestration of phosphoinositides that mediate granule fusion at the plasma membrane.
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