The ubiquitously expressed Na + /H + exchanger (NHE1) plays an important role in the regulation of the intracellular pH. Induction of NHE activity by phorbol esters and inhibition of growth factor-mediated stimulation of the NHE by protein kinase C (PKC) inhibitors suggest an implication of PKCs in the regulation of the NHE. Expression of PKC isotypespecific dominant negative and constitutively active mutants or downregulation of PKC by isotype-specific antisense oligonucleotides revealed that stimulation by epidermal growth factor (EGF) or phorbol ester of the NHE in NIH3T3 cells is a PKCK Kspecific effect. Elevation of cytoplasmic calcium by a Ca 2+ ionophore or thapsigargin causes a growth factor-independent stimulation of the NHE predominantly mediated by calcium/ calmodulin kinase II. It is concluded that in NIH3T3 cells overexpressing the EGF receptor (EGFR6 cells), EGF requires cPKCK K for the activation of the NHE, while calcium/calmodulindependent kinases are essential in thapsigargin induced stimulation of the NHE. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

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