Signal transduction in CHO cells stably transfected with domain-selective forms of murine ACE
Autor: | Maolian Gong, Xiaoou Sun, Jenny Eichhorst, Brit Rentzsch, Kristin Pankow, Björn Maul, Gisela Papsdorf, Wolf-Eberhard Siems, Michael Bader |
---|---|
Rok vydání: | 2009 |
Předmět: |
Clinical Biochemistry
Angiotensin-Converting Enzyme Inhibitors CHO Cells Peptidyl-Dipeptidase A Transfection Biochemistry Mice Cricetulus Allosteric Regulation Catalytic Domain Cricetinae Animals Humans Molecular Biology Cells Cultured chemistry.chemical_classification biology Chemistry Chinese hamster ovary cell c-jun JNK Mitogen-Activated Protein Kinases Endothelial Cells Angiotensin-converting enzyme biology.organism_classification Cell biology Enzyme Mutation biology.protein Biocatalysis Signal transduction Intracellular Signal Transduction |
Zdroj: | Biological chemistry. 391(2-3) |
ISSN: | 1437-4315 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |