Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells
Rizzo, M.T. ; Tricot, G. ; Hoffman, R. ; Jayarams, H.N. ; Weber, G. ; Garcia, J.G.N. ; English, D.
Amsterdam : Elsevier
Amsterdam : Elsevier
ISSN: |
0898-6568
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Keywords: |
G-proteins ; guanine nucleotides ; inosine monophosphate dehydrogenase inhibitors ; signal-transduction
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Source: |
Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
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Topics: |
Biology
Medicine
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Type of Medium: |
Electronic Resource
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URL: |
_version_ | 1798292091832369152 |
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autor | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. |
autorsonst | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. |
book_url | http://linkinghub.elsevier.com/retrieve/pii/0898-6568(90)90073-J |
datenlieferant | nat_lic_papers |
fussnote | Taken together, the above reports indicate that the IMP dehydrogenase inhibitors are valuable probes for investigation of the biological functions of guanine nucleotides in intact cells. While these agents have minor effects on levels of other nucleotides and enzymes, non-specific effects can be monitored by addition of guanine or guanosine to provide substrates for the salvage pathway of guanine nucleotide synthesis. The most important question yet to be resolved in employing these agents is why incomplete depletion of intracellular guanine nucleotides results in such dramatic effects on G-protein function. Since the level of GTP in resting cells is approximately 0.5 mM, even a 90% reduction in GTP levels should leave enough nucleotide to adequately activate most known G-proteins, as the latter display high binding affinities for guanine nucleotides in cell free systems. Several explanations have been proposed to account for this disparity. Much of the intracellular guanine nucleotide may be bound or compartmentalized and therefore unable to interact with certain G-proteins. Possibly, G-proteins in the intracellular environment possess a much lower affinity for GTP that they do in cell free system. It may be to the cells' advantage that relatively minor fluctuations in levels of GTP result in pronounced alterations in the biological function of G-proteins as this effect may provide a physiologically important mechanism for the regulation of G-proteins in vivo. Further studies are necessary to clarify the mechanisms involved in the regulation of the biological function of G-proteins and oncogene products by guanine nucleotides in intact cells. |
hauptsatz | hsatz_simple |
identnr | NLZ187369917 |
issn | 0898-6568 |
journal_name | Cellular Signalling |
materialart | 1 |
package_name | Elsevier |
publikationsort | Amsterdam |
publisher | Elsevier |
reference | 2 (1990), S. 509-519 |
schlagwort | G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction |
search_space | articles |
shingle_author_1 | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. |
shingle_author_2 | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. |
shingle_author_3 | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. |
shingle_author_4 | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. |
shingle_catch_all_1 | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction 0898-6568 08986568 Elsevier |
shingle_catch_all_2 | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction 0898-6568 08986568 Elsevier |
shingle_catch_all_3 | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction 0898-6568 08986568 Elsevier |
shingle_catch_all_4 | Rizzo, M.T. Tricot, G. Hoffman, R. Jayarams, H.N. Weber, G. Garcia, J.G.N. English, D. Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction G-proteins guanine nucleotides inosine monophosphate dehydrogenase inhibitors signal-transduction 0898-6568 08986568 Elsevier |
shingle_title_1 | Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells |
shingle_title_2 | Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells |
shingle_title_3 | Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells |
shingle_title_4 | Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells |
sigel_instance_filter | dkfz geomar wilbert ipn albert fhp |
source_archive | Elsevier Journal Backfiles on ScienceDirect 1907 - 2002 |
timestamp | 2024-05-06T08:43:01.011Z |
titel | Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells |
titel_suche | Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells Taken together, the above reports indicate that the IMP dehydrogenase inhibitors are valuable probes for investigation of the biological functions of guanine nucleotides in intact cells. While these agents have minor effects on levels of other nucleotides and enzymes, non-specific effects can be monitored by addition of guanine or guanosine to provide substrates for the salvage pathway of guanine nucleotide synthesis. The most important question yet to be resolved in employing these agents is why incomplete depletion of intracellular guanine nucleotides results in such dramatic effects on G-protein function. Since the level of GTP in resting cells is approximately 0.5 mM, even a 90% reduction in GTP levels should leave enough nucleotide to adequately activate most known G-proteins, as the latter display high binding affinities for guanine nucleotides in cell free systems. Several explanations have been proposed to account for this disparity. Much of the intracellular guanine nucleotide may be bound or compartmentalized and therefore unable to interact with certain G-proteins. Possibly, G-proteins in the intracellular environment possess a much lower affinity for GTP that they do in cell free system. It may be to the cells' advantage that relatively minor fluctuations in levels of GTP result in pronounced alterations in the biological function of G-proteins as this effect may provide a physiologically important mechanism for the regulation of G-proteins in vivo. Further studies are necessary to clarify the mechanisms involved in the regulation of the biological function of G-proteins and oncogene products by guanine nucleotides in intact cells. |
topic | W WW-YZ |
uid | nat_lic_papers_NLZ187369917 |