Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells

ISSN:
0898-6568
Keywords:
G-proteins ; guanine nucleotides ; inosine monophosphate dehydrogenase inhibitors ; signal-transduction
Source:
Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
Topics:
Biology
Medicine
Type of Medium:
Electronic Resource
URL:
_version_ 1798292091832369152
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