CommentariesMolecular consequences of human mast cell activation following immunoglobulin E–high-affinity immunoglobulin E receptor (IgE–FcϵRI) interaction
Section snippets
FcϵRI expression
FcϵRI belongs to the family of multi-subunit immune response receptors that do not have intrinsic kinase activity, but associate reversibly with PTK 8, 9. In its “classical” form, FcϵRI is expressed on the mast cell as a heterotetramer comprising α-, β-, and two γ-chains (Fig. 1). The binding site for IgE lies within the α-chain, which therefore confers ligand recognition and constitutes the major extracellular component of FcϵRI. The α-chain carries seven N-linked glycosylation sites, which
FcϵRI signal transduction
In the following we attempt to give a concise summary of the signaling pathways activated through FcϵRI cross-linking and their possible interactions. We will discuss the pathways separately FIG. 1, FIG. 2, FIG. 3, FIG. 4 and then bring them together in a summary (Fig. 5). This review is based essentially on findings in the rat basophilic leukemia (RBL) cell line, which is the predominant model system for studies on FcϵRI signal transduction. It remains to be shown how well the signaling
Conclusion
Finally, the signaling pathways discussed above are brought together in Fig. 5, providing a summary of ways in which the cascades may interact. However, since the parts of this mosaic are pieced together from results obtained with various experimental models, the relative contributions and importance of the individual components in human mast cells remain to be determined.
References (114)
- et al.
The human mast cell
J Allergy Clin Immunol
(1997) - et al.
Enhanced expression of high-affinity IgE receptor (FcϵRI) α chain in human allergen-induced rhinitis with co-localization to mast cells, macrophages, eosinophils, and dendritic cells
J Allergy Clin Immunol
(1997) - et al.
Expression and function of the high-affinity receptor for IgE in asthma
- et al.
Glycosylation of human truncated FcϵRI α chain is necessary for efficient folding in the endoplasmic reticulum
J Biol Chem
(1995) - et al.
New nomenclature for the Reth motif (or ARH1/TAM/ARAM/YXXL)
Immunol Today
(1995) - et al.
Signal transduction through the conserved motifs of the high affinity IgE receptor FcϵRI
Semin Immunol
(1995) - et al.
The FcϵRIβ subunit functions as an amplifier of FcϵRIγ-mediated cell activation signals
Cell
(1996) FcϵRI on antigen-presenting cells
Curr Opin Immunol
(1996)- et al.
Membrane organization in immunoglobulin E receptor signaling
Curr Opin Chem Biol
(1999) - et al.
Protein tyrosine phosphorylation as a mechanism of signalling in mast cells and basophils
Cell Signal
(1995)
Downstream signals initiated in mast cells by FcϵRI and other receptors
Curr Opin Immunol
Syk is activated by phosphotyrosine-containing peptides representing the tyrosine-based activation motifs of the high affinity receptor for IgE
J Biol Chem
The negative signaling molecule SH2 domain-containing inositol-polyphosphate 5-phosphatase (SHIP) binds to the tyrosine-phosphorylated β subunit of the high affinity IgE receptor
J Biol Chem
Role of phosphatidylinositol 3-kinase in degranulation induced by IgE-dependent and -independent mechanisms in rat basophilic RBL-2H3 (ml) cells
Cell Signal
Regulation of the calmodulin-stimulated protein phosphatase, calcineurin
J Biol Chem
Aggregation of the FcϵRI in mast cells induces the synthesis of Fos-interacting protein and increases its DNA binding-activityThe dependence on protein-kinase C-β
J Biol Chem
FcϵRI-mediated induction of nuclear factor of activated T-cells
J Biol Chem
Tec family protein-tyrosine kinases and pleckstrin homology domains in mast cells
Immunol Lett
Bruton’s tyrosine kinase-mediated interleukin-2 gene activation in mast cells. Dependence on the c-Jun N-terminal kinase activation pathway
J Biol Chem
SHIP modulates immune receptor responses by regulating membrane association of Btk
Immunity
Reconstitution of high affinity IgE receptor-mediated secretion by transfecting protein tyrosine kinase pp125FAK
J Biol Chem
Single-cell observation of calcium signals in T cells and antigen-presenting cells during antigen presentation
Immunol Lett
Activation of protein-tyrosine kinase Pyk2 is downstream of Syk in FcϵRI signaling
J Biol Chem
The Ras-related GTPase Rac1 binds tubulin
J Biol Chem
The inositol 5′-phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation
J Biol Chem
Tyrosine phosphorylation of the vav proto-oncogene product links FcϵRI to the Rac1-JNK pathway
J Biol Chem
The protein-tyrosine phosphatase SHP-2 associates with tyrosine-phosphorylated adhesion molecule PECAM-1 (CD31)
J Biol Chem
Aggregation of the high affinity IgE receptor results in the tyrosine phosphorylation of the surface adhesion protein PECAM-1 (CD31)
J Biol Chem
Vav links antigen-presentation signaling to the actin cytoskeleton
Semin Immunol
Syk-dependent phosphorylation of ShcA potential link between FcϵRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2
J Biol Chem
Association of a p95 Vav-containing signaling complex with the FcϵRI γ-chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex
J Biol Chem
SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells
J Biol Chem
Ras—a versatile cellular switch
Curr Opin Genet Dev
The complexity of Raf-1 regulation
Curr Opin Cell Biol
Regulation of Ras-mediated signalingMore than one way to skin a cat
Trends Biochem Sci
The functions of five distinct mammalian phospholipase A2s in regulating arachidonic acid release. Type IIA and type V secretory phospholipase A2s are functionally redundant and act in concert with cytosolic phospholipase A2
J Biol Chem
Modulation of cell signalling by ceramides
Biochim Biophys Acta
Regulation of phospholipase C δ1 by sphingosine
Biochim Biophys Acta
Sphingosine-1-phosphate, a metabolite of sphingosine, increases phosphatidic acid levels by phospholipase D activation
J Biol Chem
The sphingomyelin pathway in tumor necrosis factor and interleukin-1 signaling
Cell
Aggregation of IgE receptors in rat basophilic leukemia 2H3 cells induces tyrosine phosphorylation of the cytosolic protein-tyrosine phosphatase HePTP
J Biol Chem
Immunoreceptor tyrosine-based inhibition motifs
Immunol Today
The anti-ganglioside monoclonal antibody AA4 induces protein tyrosine phosphorylations, but not degranulation, in rat basophilic leukemia cells
J Biol Chem
Cell adherence to fibronectin and the aggregation of the high affinity immunoglobulin E receptor synergistically regulate tyrosine phosphorylation of 105–115-kDa proteins
J Biol Chem
Differential effects of the protein kinase C activator phorbol 12-myristate 13-acetate on calcium responses and secretion in adherent and suspended RBL-2H3 mucosal mast cells
J Biol Chem
Interleukin-4 promotes the development of tryptase and chymase double-positive human mast cells accompanied by cell maturation
Blood
Different isozymes of protein kinase C mediate feedback inhibition of phospholipase C and stimulatory signals for exocytosis in rat RBL-2H3 cells
J Biol Chem
Ca2+-dependent and Ca2+-independent isozymes of protein kinase C mediate exocytosis in antigen-stimulated rat basophilic RBL-2H3 cells. Reconstitution of secretory responses with Ca2+ and purified isozymes in washed permeabilized cells
J Biol Chem
Mucosal inflammation in asthma
Am Rev Respir Dis
Mast cell ontogeny and apoptosis
Exp Dermatol
Cited by (52)
Sargahydroquinoic acid isolated from Sargassum serratifolium as inhibitor of cellular basophils activation and passive cutaneous anaphylaxis in mice
2022, International ImmunopharmacologyCitation Excerpt :Basophils and mast cells can be activated by various stimuli such as immunoglobulin E, com 48/80, and PMACI. PMACI is known to activate immune cells via various pathways [2–4]. Recently, the search for biologically active antiallergic materials has garnered much attention.
Anti-atopic dermatitis effects of dictamni cortex: Studies on in vitro and in vivo experimental models
2021, PhytomedicineCitation Excerpt :Some key pathways involved in the intracellular free Ca2+ level were affected by DCE, including Lyn, Syk and PLCγs pathways. Activation of Lyn induces phosphorylation of the Syk kinase, thereby activating the PLCγs, which finally results in Ca2+ mobilization and mast cell degranulation (Reischl et al., 1999). Besides, activated Syk also leads to the phosphorylation of MAPKs, which are involved in the cytokines gene transcription and secretion of allergic mediators (Itoh et al., 2008).
Inhibition of mast cell degranulation by melanin
2019, Biochemical PharmacologyCitation Excerpt :FcεRI signaling has been reviewed in detail by Sibilano et al. [31]. FcεRI-mediated activation in mast cells causes activation of Src family kinases (Lyn, Syk), phospholipase C gamma (PLCγ), PI3K, protein kinase C (PKC), nonselective Ca2+ channels, members of the MAPK family, and transcription factors including NF-κB [32–36]. To examine the inhibitory mechanism of melanin on IgE-mediated degranulation, we next investigated the activation of intracellular signaling molecules in RBL-2H3 cells.
Identification of anti-allergic effect of Clonorchis sinensis-derived protein venom allergen-like proteins (CsVAL)
2014, Biochemical and Biophysical Research CommunicationsCitation Excerpt :In addition, FcεRI cross-linking on mast cells activates early signaling cascades that leads to recruitment of the non-receptor tyrosine kinase, Lyn, to the receptor complex. Lyn activation induces maximum FcεRI aggregation through the phosphorylation of receptor subunits and simultaneous activation of signaling molecules such as phospholipase Cγ, which is important for activation of protein kinase C (PKC) isoforms required for optimal degranulation [8,10,13]. Lyn phosphorylation also leads to activation of mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK, that regulate the production of inflammatory cytokines [8,10,11].
Cyclic guanosine monophosphate dependent pathway contributes to human mast cell inhibitory actions of the nitric oxide donor, diethylamine NONOate
2010, European Journal of Pharmacology