SCREENING A HYDROXYSTILBENE LIBRARY FOR SELECTIVE-INHIBITION OF THE B-CELL ANTIGEN RECEPTOR KINASE CASCADE

Protein tyrosine phosphorylation is a key post-translational modificat ion used by eukaryotic cells in receptor mediated signal transduction. Selective inhibition of cellular phosphorylation would aid efforts to elucidate the individual events in a signaling pathway A combinatoria l library of putative kinase inhibitors has been screened using an ant iphosphotyrosine blotting assay that can detect inhibition of individu al phosphorylation events in whole cells. One member of the library, 3 -hydroxy-4-methoxy-4'-nitro-rrans-stilbene (2B). has been found to sel ectively disrupt the phosphorylation of several proteins in the B cell receptor mediated cascade while not affecting other cellular phosphor ylation events. The kinase specificity of stilbene 2B is compared to k nown natural and synthetic kinase inhibitors. (C) 1997 Elsevier Scienc e Ltd.