Critical role of protein kinase C α and calcium in growth factor induced activation of the Na+/H+ exchanger NHE1
- 30 May 2002
- journal article
- Published by Wiley in FEBS Letters
- Vol. 521 (1-3) , 205-210
- https://doi.org/10.1016/s0014-5793(02)02867-3
Abstract
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 PKC(alpha)-specific 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 cPKC(alpha) for the activation of the NHE, while calcium/calmodulin-dependent kinases are essential in thapsigargin induced stimulation of the NHE.Keywords
This publication has 19 references indexed in Scilit:
- Transcriptional activation of c-fos by oncogenic Ha-Ras in mouse mammary epithelial cells requires the combined activities of PKC-λ, ε and ζThe EMBO Journal, 1998
- The p42/p44 Mitogen-activated Protein Kinase Cascade Is Determinant in Mediating Activation of the Na+/H+ Exchanger (NHE1 Isoform) in Response to Growth FactorsPublished by Elsevier ,1997
- Differential Ca2+ Signaling Induced by Activation of the Epidermal Growth Factor and Nerve Growth Factor ReceptorsJournal of Biological Chemistry, 1996
- Gα13 Stimulates Na+-H+ Exchange through Distinct Cdc42-dependent and RhoA-dependent PathwaysJournal of Biological Chemistry, 1996
- [49] Derivation of embryonic stem cell linesPublished by Elsevier ,1993
- Growth Factors Induce Phosphorylation of the Na + /H + Antiporter, a Glycoprotein of 110 kDScience, 1990
- Molecular cloning, primary structure, and expression of the human growth factor-activatable antiporterCell, 1989
- Activation of Na+/H+ exchange in cultured fibroblasts: synergism and antagonism between phorbol ester, Ca2+ ionophore, and growth factors.Proceedings of the National Academy of Sciences, 1985
- Role of protein kinase C in transmembrane signalingJournal of Cellular Biochemistry, 1985
- Phorbol ester and diacylglycerol mimic growth factors in raising cytoplasmic pHNature, 1984