Cutting edge: Extracellular signal-regulated kinase activates Syk: A new potential feedback regulation of Fc epsilon receptor signaling

The protein tyrosine kinase Syk is an essential element in several cascades coupling Ag receptors to cell responses. Syk and the mitogen-activated pro tein kinase extracellular signal-regulated kinase 1 (ERK1) were found to fo rm a tight complex in both resting and Ag-stimulated rat mucosal-type mast cells (rat basophilic leukemia 2H3 cell line RBL-2H3). A direct serine phos phorylation and activation of Syk by ERK was observed in in vitro experimen ts. Moreover the mitogen-activated protein kinase/extracellular signal-regu lated protein kinase (ERK) kinase (MEK) inhibitors markedly decreased the A g-induced phosphorylation of the tyrosyl residues of Syk and its activation as well as suppressed the degranulation of the cells. These results sugges t a positive feedback regulation of Syk by ERK in the cascade coupling the type 1 Fee receptor to the secretory response of mast cells; hence, the exi stence of a novel type of cross-talk between protein serine/threonine kinas es and protein tyrosine kinases is suggested.