CCK2 (CCKB/gastrin) receptor mediates rapid protein kinase D (PKD) activation through a protein kinase C-dependent pathway

Addition of gastrin or cholecystokinin octapeptide (CCK-8) to cultures of R at-1 cells stably transfected with the CCK2 (CCKB/gastrin) receptor induced protein kinase D (PKD) activation that was detectable within 1 min and rea ched a maximum (similar to 10-fold) after 2.5 min of hormonal stimulation. Half-maximal PKD activation for both CCK-8 and gastrin mas achieved at 10 n M. Treatment with various concentrations of the selective PKC inhibitors Ro 31-8220 or GF-I potently blocked PKD activation induced by subsequent addi tion of CCK-8 in a concentration-dependent fashion. Our results indicate th at PKC-dependent PKD activation is a novel early event in the action of gas trin and CCK-8 via CCK2 receptors. (C) 2001 Federation of European Biochemi cal Societies. Published by Elsevier Science B.V. All rights reserved.