Ontology type: schema:ScholarlyArticle
2002-08-28
AUTHORSMarkus Klinger, Mandy Kuhn, Herwig Just, Eduard Stefan, Timothy Palmer, Michael Freissmuth, Christian Nanoff
ABSTRACT. The A2A-adenosine receptor has an extended carboxy terminus (~120 amino acids), the role of which is poorly defined. In human endothelial cells and in HEK293 cells, the A2A-receptor controls at least two independent signalling pathways, i.e. increased cyclic adenosine 3′,5′-monophosphate (cAMP) formation via its cognate G protein Gs and increased phosphorylation of mitogen-activated protein kinase (MAP kinase) by recruiting p21ras. In order to address the role of the carboxy terminus in signal transfer, we generated HEK293 cells that stably expressed the full-length (wt) receptor and truncated versions [A2A-R(1-360) and A2A-R(1-311)] at comparable levels (~0.5 pmol/mg) in the plasma membrane. The effects of truncation were divergent with respect to the two effectors regulated by the receptor. In intact cells carrying A2A-R(wt) and A2A-R(1-360), cAMP accumulation was more potently activated by an A2A-agonist than in cells expressing A2A-R(1-311). Similarly, A2A-R(wt) and A2A-R(1-360) – but not A2A-R(1-311) – caused constitutive (=agonist-independent) elevation of cAMP which was reversed by the addition of A2A-antagonists. In membranes prepared from these cells, however, the three receptors displayed no constitutive activity in stimulating adenylyl cyclase and they did not differ in apparent agonist affinity. Truncation of the A2A-receptor did also not decrease the potency of an A2A-agonist to stimulate MAP kinase in intact cells. We conclude that the carboxy terminus defines both (a) the level of constitutive activity, i.e. the equilibrium R↔R*, in intact cells only, indicating a role for a component that is lost upon cell lysis, and (b) the efficiency of signal transfer in alternative pathways. More... »
PAGES287-298
http://scigraph.springernature.com/pub.10.1007/s00210-002-0617-z
DOIhttp://dx.doi.org/10.1007/s00210-002-0617-z
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1015763478
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/12237741
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