Linked Life Data

7890682

Source:http://linkedlifedata.com/resource/pubmed/id/7890682

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1995-4-14
pubmed:abstractText
The expression of human muscarinic acetylcholine receptors (mAChRs) in NIH 3T3 cells has been used as a model for studying proliferative signaling through G protein-coupled receptors. In this biological system, the m1 class of mAChRs can effectively transduce mitogenic signals (Stephens, E.V., Kalinec, G., Brann, M.R., and Gutkind, J.S. (1993) Oncogene 8, 19-26) and induce malignant transformation if persistently activated (Gutkind, J.S., Novotny, E.A., Brann, M.R., and Robbins, K.C. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4703-4708). Moreover, available evidence suggests that the m1-signaling pathway converges at the level of p21ras with that emerging from tyrosine kinase receptors (Crespo, P., Xu, N., Simonds, W.F., and Gutkind, J.S. (1994) Nature 369, 418-420). To explore nuclear events involved in growth regulation by G protein-coupled receptors in this setting, we compared the effect of platelet-derived growth factor (PDGF) and the cholinergic agonist, carbachol, on the expression of mRNA for members of the jun and fos family of nuclear proto-oncogenes. We found that activation of m1 receptors by carbachol induces the expression of a distinct set of nuclear transcription factors. In particular, carbachol caused a much greater induction of c-jun mRNA and AP-1 activity. These responses did not correlate with protein kinase C stimulation nor with the activation of mitogen-activated protein (MAP) kinases. Recently, it has been shown that a novel family of kinases structurally related to MAP kinases, stress-activated protein kinases, or Jun kinases (JNKs), phosphorylate in vivo the amino-terminal transactivating domain of the c-Jun protein, thereby increasing its transcriptional activity. In view of our results, this observation prompted us to ask whether m1 and PDGF can differentially activate JNKs. Here, we show that m1 mAChRs can induce a remarkable increase in JNK activity, which was temporally distinct from that of MAP kinase and was entirely protein kinase C independent. In contrast, PDGF failed to activate JNK in these cells, although it stimulated MAP kinase to an extent even greater than that for carbachol. These findings demonstrate that G protein-coupled receptors can signal through pathways leading to the activation of JNK, thus diverging at this level with those signaling routes utilized by tyrosine kinase receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
270
pubmed:geneSymbol
c-fos, c-jun, egr-1, fos, fra-1, jun, jun B, jun D
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5620-4
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7890682-3T3 Cells, pubmed-meshheading:7890682-Animals, pubmed-meshheading:7890682-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:7890682-Carbachol, pubmed-meshheading:7890682-Cell Division, pubmed-meshheading:7890682-Enzyme Activation, pubmed-meshheading:7890682-Gene Expression, pubmed-meshheading:7890682-Genes, Immediate-Early, pubmed-meshheading:7890682-Genes, fos, pubmed-meshheading:7890682-Genes, jun, pubmed-meshheading:7890682-Humans, pubmed-meshheading:7890682-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:7890682-Mice, pubmed-meshheading:7890682-Mitogen-Activated Protein Kinases, pubmed-meshheading:7890682-Platelet-Derived Growth Factor, pubmed-meshheading:7890682-Protein Kinase C, pubmed-meshheading:7890682-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:7890682-Receptors, Muscarinic, pubmed-meshheading:7890682-Signal Transduction, pubmed-meshheading:7890682-Tetradecanoylphorbol Acetate, pubmed-meshheading:7890682-Transcription Factor AP-1, pubmed-meshheading:7890682-Transfection
pubmed:year
1995
pubmed:articleTitle
Transforming G protein-coupled receptors potently activate JNK (SAPK). Evidence for a divergence from the tyrosine kinase signaling pathway.
pubmed:affiliation
Molecular Signaling Unit, NIDR, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article