Related Experiment Video
Updated: May 8, 2026
11:31
Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
Published on: July 4, 2018
A role for prohibitin in mast cell activation: location matters
Hajime Yurugi1, Krishnaraj Rajalingam
11Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kitaku, Kyoto 603-8555, Japan.
Science Signaling
|September 12, 2013
Summary
Prohibitin 1 (PHB1) protein is crucial for mast cell activation during allergic reactions. Upon antigen stimulation, PHB1 moves to the plasma membrane, triggering degranulation and cytokine release.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Prohibitin 1 (PHB1) and PHB2 are vital proteins regulating fundamental cellular processes.
- Plasma membrane-associated PHBs are implicated in tumor metastasis, viral entry, and immune cell activation.
Purpose of the Study:
- To investigate the role of PHB1 in mast cell activation and immunoglobulin E (IgE)-mediated allergic reactions.
Main Methods:
- Immunofluorescence microscopy to track PHB1 localization.
- Co-immunoprecipitation to identify protein complexes.
- Biochemical assays to assess Syk kinase activation and mast cell degranulation.
Main Results:
- PHB1 localizes to mast cell granules and translocates to plasma membrane lipid rafts upon antigen stimulation.
- PHB1 forms a complex with FcεRIγ and Syk, leading to Syk activation.
- PHB1 phosphorylation by Lyn and palmitoylation are essential for its membrane association and function.
- Mast cell degranulation and cytokine secretion are triggered by this signaling cascade.
Conclusions:
- PHB1 plays a novel and critical role in the proximal signaling events of FcεRI activation by IgE in mast cells.
- This study elucidates a new mechanism in allergic reaction pathways involving PHB1.
- PHB1 represents a potential therapeutic target for allergic diseases.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...