Effects of the indolocarbazole 3744W on the tyrosine kinase activity of the cytoplasmic domain of the platelet-derived growth factor beta-receptor

The cytoplasmic domain of the platelet-derived growth factor (PDGF) beta-re ceptor was expressed in insect cells by using a baculovirus system. The res ulting protein was a constitutively active tyrosine kinase that could phosp horylate both protein and peptide substrates, A recently identified potent and selective inhibitor of intact PDGF receptor autophosphorylation, 3744W, inhibited the autophosphorylation of the cytoplasmic domain both in vitro (IC50 1.8 +/- 0.12 mu M) and within intact insect cells (IC50 2.0 mu M). Ho wever, under identical assay conditions, 3744W did not inhibit the phosphor ylation of the synthetic polymeric peptide poly(Glu(4)Tyr(1)) even at conce ntrations as high as 100 mu M. These results suggest that, although 3744W i nhibits PDGF receptor autophosphorylation directly, it can discriminate bet ween phosphate acceptor substrates. CELL SIGNAL 11;2:95-100, 1999. (C) 1998 Elsevier Science Inc.