Schematic diagram of possible IgE-mediated signaling pathways in basophils.
Following high-affinity IgE-receptor cross-linking, various tyrosine kinases are activated, including Lyn and Syk, which consequently lead to the activation of PI 3-kinases, ERK-associated MAP kinases (Vav, Ras, Raf1, MEK), and PLC. PI 3-kinase targets include both p38 MAP kinase (p38) and Rac/Rho GTPases (Rac/Rho), which are involved in cytokine production. Further, Rac/Rho affect the cytoskeletal processes100 during degranulation as well as extracellular signal–related kinase-activating kinase (MEK). IgE-dependent ERK activation in basophils is largely limited to controlling LTC4 generation; PKC, activated by diacylglycerol (DAG) as a result of hydrolysis of PIP2 by PLC, is involved in degranulation. PKC may also affect cytokine transcription, although the mechanism is not yet clear. The release of calcium from intracellular stores by IP3 together with the influx of the ion through calcium channels affects degranulation, PLA2 translocation, and calcineurin activity. Thicker print is used to highlight what is currently known in human basophils. The remaining has been extrapolated from studies with rodent mast cells or cell lines.
