AGGREGATION OF THE FC-EPSILON-RI IN MAST-CELLS INDUCES THE SYNTHESIS OF FOS-INTERACTING PROTEIN AND INCREASES ITS DNA-BINDING ACTIVITY - THE DEPENDENCE ON PROTEIN-KINASE C-BETA

The ability of c-Fos to dimerize with various proteins creates transcr iption complexes which can exert their regulatory function on a variet y of genes. One of the transcription factors that binds to c-Fos is th e newly discovered Fos-interacting protein (FIP). In this report we pr esent evidence for the regulation of the synthesis of FIP by a physiol ogical stimulus. We found that the aggregation of the mast cell high a ffinity receptor for IgE (Fc epsilon RI) induced the synthesis of FIP and increased its DNA binding activity. Moreover, down-regulation of t he isoenzyme protein kinase C-beta (PKC-beta) by a specific antisense phosphorothioate oligonucleotide resulted in profound inhibition of FI P Fos DNA binding activity. Thus, aggregation of the Fc epsilon RI on mast cells elicits a PKC-beta dependent signaling pathway which regula tes FIP-Fos DNA binding activity.