Fc receptor-mediated signal transduction

Receptors for the Fc domain of IgG (Fc gamma Rs) on leukocytes mediate a pleiotropic response following cross-linking by immune complexes. Signaling events following cross-linking of B and T cell antigen receptors, Fc epsilon RI, and Fc gamma Rs share common elements. In each, signaling is initiated by receptor cross-linking by antigen or immune complexes and results in the activation of src family kinases and ZAP-70-related tyrosine kinases, which associate with members of the receptor complex. Subsequent events include phosphorylation on tyrosine of multiple cellular substrates including phospholipase C gamma 1 and PI3-kinase. The [Ca2+]i flux is an event secondary to phospholipase C gamma 1 activation. Protein tyrosine kinase inhibitors block both early events such as [Ca2+]i flux and the later effects of cytokine release and cellular proliferation.