Signal transduction in CHO cells stably transfected with domain-selective forms of murine ACE
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Xiaoou Sun
Abstract
Membrane-bound human angiotensin-converting enzyme (ACE) has been reported to initiate intracellular signaling after interaction with substrates or inhibitors. Somatic ACE is known to contain two distinct, extracellular catalytic centers. We analyzed the signal transduction mechanisms in cells transfected with different forms of murine ACE (mACE) and investigated whether the two domains are similarly involved in these processes. For this purpose, CHO cells were stably transfected with mACE or with its domain-selective mutants. In addition to these modified cellular models, human umbilical vein endothelial cells were used in this study. Signal transduction molecules such as JNK and c-Jun were analyzed after activation of cells with several ACE substrates and inhibitors. ACE-targeting compounds such as substrates, inhibitors, or even the ACE product angiotensin-II induce in mACE-expressing cells a signal transduction response. These processes are also evoked by partially inactivated forms of mACE and finally result in an enhanced cyclooxygenase-2 transcription. Surprisingly, the membrane-bound ACE activity is also influenced by ACE-targeted interventions. Our data suggest that the two catalytic domains of mACE do not function independently but that the signal transduction is influenced by negative cooperativity of the two catalytic domains. This study underlines that ACE indeed has receptor-like properties which occur in a species-specific manner.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- EDITORIAL
- Highlight: Signal Transduction and Disease
- HIGHLIGHT: SIGNAL TRANSDUCTION AND DISEASE
- Phosphorylase and the origin of reversible protein phosphorylation
- β-Catenin as a multilayer modulator of zonal cytochrome P450 expression in mouse liver
- Glycome profiling using modern glycomics technology: technical aspects and applications
- Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity
- MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway
- Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function
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- 6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent synthesis of small de novo products
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- Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation
- Peptides from the Mycobacterium tuberculosis Rv1980c protein involved in human cell infection: insights into new synthetic subunit vaccine candidates
- The epimerase activity of anthocyanidin reductase from Vitis vinifera and its regiospecific hydride transfers
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- CELL BIOLOGY AND SIGNALING
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