Cooperation of adapter molecules in proximal signaling cascades during allergic inflammation
Taku Kambayashi,
David F. LaRosa,
Michael A. Silverman,
Gary A. Koretzky,
Taku Kambayashi
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Search for more papers by this authorDavid F. LaRosa
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Search for more papers by this authorMichael A. Silverman
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Search for more papers by this authorGary A. Koretzky
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Search for more papers by this authorTaku Kambayashi,
David F. LaRosa,
Michael A. Silverman,
Gary A. Koretzky,
Taku Kambayashi
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Search for more papers by this authorDavid F. LaRosa
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Search for more papers by this authorMichael A. Silverman
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Search for more papers by this authorGary A. Koretzky
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Search for more papers by this authorGary Koretzky
Abramson Family Cancer Research InstituteUniversity of Pennsylvania415 BRB II/III, 421 Curie BoulevardPhiladelphia, PA 19104-6160, USATel.: +1 215 746 5522Fax: +1 215 746 5525e-mail: [email protected]
Abstract
Summary: Activation of mast cells through their high-affinity immunoglobulin E receptor (FcεRI) plays an important role in allergic disorders. Other mast cell-activating stimuli, such as Toll-like receptor (TLR) ligands, synergize with FcεRI to enhance allergic inflammation. Thus, there is much interest in understanding how signaling occurs downstream of these receptors. One key event for FcεRI-mediated mast cell activation is the inducible formation of multimolecular proximal signaling complexes. These complexes are nucleated by adapter proteins, scaffolds that localize various signaling molecules through their multiple molecule-binding domains. Here we review recent findings in proximal signaling cascades with an emphasis on how adapter molecules cooperate with each other to generate an optimal signal in mast cells, and we discuss how signals crosstalk between FcεRI and TLRs in enhancing mast cell activation. Deciphering the molecular mechanisms leading to mast cell activation will hopefully bring new ideas for the development of novel therapeutics to control allergic diseases.
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