A REQUIREMENT FOR SYK IN THE ACTIVATION OF THE MICROTUBULE-ASSOCIATEDPROTEIN-KINASE PHOSPHOLIPASE-A(2) PATHWAY BY FC-EPSILON-R1 IS NOT SHARED BY A G-PROTEIN-COUPLED RECEPTOR

Stimulation of the mast cell line, RBL-2H3, with antigen via the tetra meric (alpha beta gamma(2)) immunoglobulin E receptor (Fc epsilon R1) leads to the activation of cytosolic phospholipase A(2) and the releas e of arachidonic acid. This pathway is dependent on the activation of the mitogen-activated protein (MAP) kinase, In this paper, we show tha t the MAP kinase/cytosolic phospholipase A(2) pathway is linked to Fc epsilon R1 via the cytosolic tyrosine kinase, Syk, and that the GDP/GT P exchange factor, Vav, might be one candidate for accomplishing this link, Cross-linking of transmembrane chimeras containing the Fc epsilo n R1 gamma motif, which is known to activate Syk, results in the tyros ine phosphorylation of Vav, activation of MAP kinase, and release of a rachidonic acid. Cross-linking of chimeras containing the Fc epsilon R 1 beta motif does not cause these events, Furthermore, stimulation of these events by antigen is enhanced by transient overexpression of a w ild-type form of Syk and blocked by overexpression of a dominant negat ive form of Syk, By contrast, stimulation via the transfected, G prote in-coupled, muscarinic mi receptor is not influenced by either form of Syk and does not result in tyrosine phosphorylation of Vav, These dat a establish unequivocally that the two types of receptor are independe ntly linked to the MAP kinase/ cytosolic phospholipase A(2) pathway an d demonstrate the existence of the Fc epsilon R1-Syk-MAP kinase pathwa y.