期刊
FEBS LETTERS
卷 521, 期 1-3, 页码 205-210出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(02)02867-3
关键词
Na+/H+ exchanger; NHE1; protein kinase C isotype; calcium; epidermal growth factor; NIH3T3
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 isotype-specific 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 PKCalpha-specific effect. Elevation of cytoplasmic calcium by a Ca2+ 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 cPKCalpha for the activation of the NHE, while calcium/calmodulin-dependent kinases are essential in thapsigargin induced stimulation of the NHE. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
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