Role of protein kinases in the regulation of growth and transport of kidney cells by prostaglandin e1

The mechanisms by which type I and type II cyclic AMP dependent protein kinase (A kinase) stimulate the growth and ths expression of differentiated transport functions of Madin Darby Orvie Kidney (MOCK) cells in hormonally defined serum free mediurti has been examined utilizing variant MDCK cells which are defective ':i either the growth or the transport response to Prostaglandin E, W.ci). PGE| stimulates the growth of MDCK cells via a cAMP mediate-J mechanism, and whether this involves Mitogen Activated (MAP) p<otein kinases is not clearly understood. PGEi also stimulates the activity of the Na,K-ATPase in MDCK cells,. This effect is lost in variant cells which are defective in type I cyclic AMP dependent protoii kinase. Regulation of the level of expression of the Na,K-ATP?se by PGE i (and cyclic AMP) occurs at least in part at the transcripu-onal level, as evidenced by nuclear runoff transcription studies, ind transient transfection studies utilizing a plasmid which contXv a Na,K-ATPase beta subunit promoter/luciferase construct. An ins raised level of expression of the Na,K-ATPase beta subunit mRNA (uoserved in PGEi treated MDCK cells) is associated with an increase in the overall rate of biosynthesis of both the alpha and the beta subunits of the Na,K-ATPase (which could possibly be explained by beta subunit excess). Ultimately, an increase in the overall level of the Na.K-ATPase . as well as increased Na.K-ATPase activity is observed.