Mast cell signaling

Mast cell signaling refers to the complex network of intracellular biochemical events that regulate the activation, degranulation, and mediator release of mast cells, which are central effectors in allergic and inflammatory responses (NIH, 1.1.1). This process is primarily triggered by the cross-linking of high-affinity IgE receptors (FcεRI) by antigens or the activation of the KIT receptor (CD117) by stem cell factor (SCF) (NIH, 1.1.2, 1.1.5). These events recruit and activate a series of intracellular kinases, including Lyn, SYK, and BTK, which propagate signals leading to calcium mobilization and the release of preformed mediators like histamine and proteases, as well as the synthesis of leukotrienes and cytokines (NIH, 1.1.3, 1.4.1). Dysregulation of these signaling pathways is a key driver of diseases such as asthma, allergic rhinitis, anaphylaxis, and mastocytosis (NIH, 1.1.1, 1.3.2). Therapeutic interventions target various nodes within this network, including the use of monoclonal antibodies to block IgE-receptor interactions, small-molecule inhibitors of KIT or downstream kinases, and mast cell stabilizers that prevent the release of pro-inflammatory substances (MDPI, 1.2.4; NIH, 1.2.1).

Other names

Mast cell activation pathwayMast cell degranulation signalingFcεRI signaling pathwayMast cell mediator release pathway

Drugs targeting mast cell signaling act by neutralizing circulating IgE to prevent receptor cross-linking, inhibiting receptor tyrosine kinases such as KIT to reduce mast cell survival and activation, blocking downstream signaling enzymes like SYK and BTK to prevent degranulation, or stabilizing the mast cell membrane to inhibit the release of inflammatory mediators.