Human immune cells express ppMCH mRNA and functional MCHR1 receptor |
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Authors: | Verlaet Myriam Adamantidis Antoine Coumans Bernard Chanas Grazyna Zorzi Willy Heinen Ernst Grisar Thierry Lakaye Bernard |
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Institution: | Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria. karl.maly@uibk.ac.at |
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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. |
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