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Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gutkind, J. Silvio Novotny, Elizabeth A. Brann, Mark R. Robbins, Keith C. |
| Copyright Year | 1991 |
| Abstract | We have evaluated the muscarinic acetylcholine family of G protein-coupled receptors (mAChRs) for their oncogenic potential. These receptors are preferentially expressed in postmitotic cells, transducing signals specified by their endogenous agonist, the neurotransmitter acetylcholine. Cells transfected with individual human mAChR genes were morphologically indistinguishable from parental NIH 3T3 cells in the absence of agonist. In contrast, when cultures were supplemented with carbachol, a stable analog of acetylcholine, foci of transformation readily appeared in m1, m3, or m5 but not in m2 or m4 mAChRs transfectants. Receptor expression was verified by ligand binding and was similar for each transfected culture. Transformation was dose-dependent and required only low levels of receptor expression. In transformation-competent cells, agonist induced phosphatidylinositol hydrolysis, whereas in m2 or m4 transfectants, receptors were coupled to the inhibition of adenylyl cyclase. These findings demonstrate that mAChRs linked to phosphatidylinositol hydrolysis can act as conditional oncogenes when expressed in cells capable of proliferation. |
| Starting Page | 41 |
| Ending Page | 45 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/88/11/4703.full.pdf |
| PubMed reference number | 1905013v1 |
| Volume Number | 88 |
| Issue Number | 11 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Analog Carbachol Cholinergic Receptors Ligand Binding Ligands M3 Mental Health Checklist M4 Additive/Preservative M5 Additive/Preservative Muscarinic Acetylcholine Receptor Neurotransmitters Oncogenes Subtype (attribute) adenylate cyclase-activating G-protein coupled receptor signaling pathway |
| Content Type | Text |
| Resource Type | Article |