Linked Life Data

12391277

Source:http://linkedlifedata.com/resource/pubmed/id/12391277

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-10-22
pubmed:abstractText
Adenosine activates four different receptors, the A(1), A(2A), A(2B), and the A(3) receptors, all of which are G protein-coupled. We have previously shown that stimulation of the human adenosine A(3) receptor can induce phosphorylation of extracellular signal-regulated kinase (ERK1/2). Here we show that the adenosine receptor agonist 5' N-ethylcarboxamidoadenosine (NECA) induces phosphorylation and activation of ERK1/2 in Chinese hamster ovary (CHO) cells expressing the human adenosine A(3) receptor (CHO A(3) cells) with the same potency. Pretreatment with pertussis toxin abolished the effect, which also could be blunted by overexpressing the betagamma-sequestering peptide beta-adrenergic receptor kinase-ct, implicating the involvement of betagamma subunits released from G(i/o) proteins. Activation of phosphatidylinositol-3-kinase (PI3K) by adenosine A(3) receptors is inferred from a dose-dependent Ser-phosphorylation of the protein kinase B (Akt). Furthermore the ERK1/2 phosphorylation was sensitive to the PI3K inhibitors wortmannin and LY294002 (2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride) and the MEK inhibitor PD98059 (2'-amino-3'-methoxyflavone), whereas chelation of Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) and long-term treatment with phorboldibutyrate did not decrease the adenosine A(3) receptor-mediated ERK1/2 phosphorylation. Thus, Ca(2+) mobilization and conventional and novel protein kinase C (PKC) isoforms are not involved in this pathway. The atypical PKCzeta was not activated by NECA and thus not involved in the A(3) receptor-mediated ERK1/2 phosphorylation. NECA stimulation of CHO A(3) cells activated the small G protein Ras and the dominant negative mutant RasS17N prevented the phosphorylation of ERK1/2. In conclusion, the adenosine A(3) receptor recruits a pathway that involves betagamma release from G(i/o), PI3K, Ras, and MEK to induce ERK1/2 phosphorylation and activation, whereas signaling is independent of Ca(2+), PKC, and c-Src.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1137-46
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12391277-Animals, pubmed-meshheading:12391277-CHO Cells, pubmed-meshheading:12391277-Cricetinae, pubmed-meshheading:12391277-Enzyme Activation, pubmed-meshheading:12391277-GTP-Binding Protein alpha Subunits, Gi-Go, pubmed-meshheading:12391277-GTP-Binding Proteins, pubmed-meshheading:12391277-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:12391277-Mitogen-Activated Protein Kinases, pubmed-meshheading:12391277-Oncogene Protein pp60(v-src), pubmed-meshheading:12391277-Pertussis Toxin, pubmed-meshheading:12391277-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12391277-Phosphorylation, pubmed-meshheading:12391277-Receptor, Adenosine A3, pubmed-meshheading:12391277-Receptors, Purinergic P1, pubmed-meshheading:12391277-Signal Transduction, pubmed-meshheading:12391277-ras Proteins
pubmed:year
2002
pubmed:articleTitle
Signaling pathway from the human adenosine A(3) receptor expressed in Chinese hamster ovary cells to the extracellular signal-regulated kinase 1/2.
pubmed:affiliation
Section of Molecular Neuropharmacology, Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden. gunnar.schulte@fyfa.ki.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't