Proximal signaling events in FcεRI-mediated mast cell activation

• Published in: Journal of allergy and clinical immunology Vol. 119; no. 3; pp. 544 - 552
• Main Authors: Kambayashi, Taku, MD, PhD, Koretzky, Gary A., MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01.03.2007
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Allergy and Immunology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity - drug therapy; Hypersensitivity - immunology; Immunopathology; Mast Cells - drug effects; Mast Cells - immunology; Medical sciences; Protein Kinase C - metabolism; Protein Structure, Tertiary; Receptors, IgE - chemistry; Receptors, IgE - genetics; Receptors, IgE - metabolism; Signal Transduction - drug effects; Src homology 2 domain-containing phosphatase 1; Linker for activation of T cell; Protein kinase C; IgE; JNK; PLC; PTK; Diacylglycerol; GBF; SHP-1; PI3K; NTAL; Protein tyrosine kinase; SHIP; PSA; Src homology 2 domain-containing leukocyte-specific phosphoprotein of 76 kd; Phosphatidylinositol-3 kinase; SLP-76; Syk; Non–T-cell activation linker; Extracellular signal-regulated kinase; allergy; PKC; Grb-associated binder 2; DAG; Gab2; s-Jun N-terminal kinase; Bruton's tyrosine kinase; Mitogen-activated protein; Gads-binding fragment; Phospholipase C; Spleen tyrosine kinase; adapter molecules; ITAM; cell signaling; Passive systemic anaphylaxis; Btk; Mast cell; FcεRI; Immunoreceptor tyrosine-based activation motif; Src homology 2-containing inositol phosphatase; MAP; LAT; ERK; Proximal; Immunopathology; Allergy; Enzyme; Transferases; FcεRI receptor; Immunoglobulin receptor; FCεRI; Signal transduction; Immunology; Protein-tyrosine kinase
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.01.017

Mast cells are central mediators of allergic diseases. Their involvement in allergic reactions is largely dependent on activation through the specific receptor for IgE (FcεRI). Cross-linking of FcεRI on mast cells initiates a cascade of signaling events that eventually results in degranulation, cytokine/chemokine production, and leukotriene release, contributing to allergic symptomology. Because of the importance of IgE in allergy, much focus has been placed on deciphering the signaling events that take place downstream of FcεRI. Studies have identified spleen tyrosine kinase as a key proximal regulator of FcεRI-mediated signaling. In this review, we discuss the multiple pathways that diverge from spleen tyrosine kinase with emphasis on the role of adapter molecules to orchestrate these signaling events. Understanding the molecular mechanisms underlying mast cell activation ideally will provide insights into the development of novel therapeutics to control allergic disease.