Abstract Antigen-induced cross-linking of immunoglobulin E (IgE) antibodies bound to the high-affinity IgE receptor (FcεRI), on mast cells results in the release of mediators that initiate an inflammatory response. This normal immune response has been abducted by immunological adap- tation, through the production of IgE antibodies to normally innocu- ous substances, to cause allergic disease. Therefore, understanding the molecular requirements in IgE-dependent mast-cell activation holds promise for therapeutic intervention in disease. Recent investigation on the functional coupling of FcεRI to the intracellular signaling appa- ratus has provided paradigm-altering insights on the importance and Key Words Allergy Cytokines Degranulation FcεRI Fyn IgE Lyn Mast cells Juan Rivera NIAMS/NIH Building 10, Room 9N228 10 Center Drive, MSC 1820 Bethesda, MD 20892-1820 E-mail: juan_rivera@nih.gov 241 © 2004 Humana Press Inc. 0257–277X/04/ 30/2:241–253/$25.00 Rethinking the Role of Src Family Protein Tyrosine Kinases in the Allergic Response New Insights on the Functional Coupling of the High Affinity IgE Receptor Immunologic Research 2004;30/2:241–253 Yasuko Furumoto Claudia Gonzalez- Espinosa Gregorio Gomez Martina Kovarova Sandra Odom Valentino Parravicini John J. Ryan a Juan Rivera* Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. a Present Address or other Affiliation: (C. G. -E). Pharmacobiology Department, CINVESTA V Zona Sur, Calzada de los Tenorios 235, Mexico D.F. CP 14330 Mexico; (V. P.), Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway Mill Hill, London NW7, 1AA, UK; (J. J. R.), Department of Biology, Virginia Commonwealth University, Richmond, VA, 23284-2012.