Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: EC:4.1.1.17 (
ornithine decarboxylase
)
6,351
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Histamine and putrescine (a precursor of polyamines) are formed by histidine decarboxylase (HDC) and
ornithine decarboxylase
(
ODC
), respectively. Within a few hours after injection of a lipopolysaccharide (LPS) into mice, HDC is induced in the liver, spleen, lung and bone marrow, and
ODC
is induced in the liver, spleen and bone marrow. Since LPS is known to stimulate the production of various cytokines, the abilities of various cytokines to induce HDC and
ODC
in the tissues of mice were examined. IL-2, IL-6, IL-8, IFN gamma and M-CSF were ineffective. IL-1 alpha, IL-1 beta, TNF alpha and TNF beta induced HDC and
ODC
, as does LPS. On the other hand,
GM-CSF
and G-CSF induced HDC and
ODC
only in the spleen and bone marrow within a few hours after their injection. These results suggest that, in addition to their roles in inflammation or immune responses, HDC and
ODC
are also involved in an early stage of hematopoiesis.
...
PMID:GM-CSF and G-CSF stimulate the synthesis of histamine and putrescine in the hematopoietic organs in vivo. 138 20
Colony-stimulating factors (CSFs) stimulate the activation and steady-state mRNA accumulation of an important regulatory enzyme for macromolecular synthesis,
ornithine decarboxylase
(
ODC
). Cloned murine CSF-dependent cell lines exhibited a rapid activation of
ODC
enzyme activity, detectable within ten minutes of stimulations with either interleukin-3 (IL-3),
GM-CSF
, or G-CSF. This early phase of enzyme activation did not require early protein or mRNA synthesis. The subsequent protracted rise in
ODC
activity occurring four to six hours after CSF treatment was dependent on increases in steady-state
ODC
mRNA accumulation and de novo protein synthesis. CSF, therefore, modulates both posttranslational activation of preexisting
ODC
and stabilization and accumulation of
ODC
mRNA. Antiproliferative signals, such as cAMP or interferon-gamma (IFN-gamma), effectively inhibited the CSF-directed increase in steady-state
ODC
mRNA. Cotreatment of the murine NSF 60.8 cell line with IFN-gamma and
GM-CSF
decreased steady-state
ODC
mRNA greater than 80% as compared with
GM-CSF
-treated cells alone. IFN treatment did not cause any appreciable destabilization of mature
ODC
mRNA, suggesting that its major effect may be at the level of
ODC
mRNA transcription or posttranscriptional processing. These data indicate that the
ODC
gene-protein system is an important molecular locus of the effects of myeloid proliferative and antiproliferation signals.
...
PMID:Myeloid growth factor(s) regulation of ornithine decarboxylase: effects of antiproliferative signals interferon-gamma and cAMP. 246 92
The polypeptide hormones governing the proliferation and differentiation of the mature immune system and hematopoiesis are collectively referred to as lymphokines. We have examined a number of biochemical and molecular events stimulated by several unique lymphokines which exhibit proliferative activity on lymphoid and myeloid cell lines. Interleukin-2 (IL-2) and several members of the colony-stimulating factors (IL-3, G-CSF, and
GM-CSF
) stimulate similar patterns of cellular phosphorylation including the prominent phosphorylation of a 68-kDa substrate present in numerous distinct lineage cell lines. The 68-kDa substrate is phosphorylated by protein kinase C on threonine residues and is primarily cytosolic. Another kinase system activated by either physiological ligand or synthetic diacylglycerol phosphorylated the 40S ribosomal protein in a dose-dependent manner. The increased phosphorylation of S6 protein was associated with enhanced chain elongation in vitro. The kinase responsible for the in situ phosphorylation, however, was not protein kinase-C (PK-C) but another physicochemically distinct Mg2+-dependent enzyme (termed S6 kinase). These studies suggested that, although PK-C was activated by diacylglycerol, another kinase, S6 kinase, was the effector enzyme involved in the phosphorylation of the 40S protein. IL-2 and all other CSFs tested stimulated the transcription of the nuclear protooncogenes c-fos, c-myc, and c-myb. In addition,
ornithine decarboxylase
mRNA accumulation was also stimulated. Phorbol esters also stimulated similar gene expression; however, cyclic AMP analog inhibited phorbol ester or ligand-induced c-myc expression and ODC mRNA accumulation. Cyclic AMP agonists are antiproliferative to all the growth factors tested. We have constructed complementary oligonucleotides, "antisense", against c-fos, c-myc, and other structural genes induced by the growth factors. Such antisense oligomers were capable of selectively deleting protein expression of the respective gene products and inhibited the biological action of the growth factors.
...
PMID:The molecular basis of immune cytokine action. 265 49
Haemopoietic growth factors stimulate a number of consensus biochemical and molecular events regardless of the specificity detailed by unique ligand and receptor structures. Analysis of three distinct colony stimulating factors, CSFs (IL-3, G-CSF,
GM-CSF
) and the lymphocytotropic growth factor IL-2 reveal remarkable similar distal subcellular biochemical signals although initial membrane 'signal transduction' may differ significantly. Both early progenitor cell growth factors, such as IL-3, and late acting factors such as CSF-1, stimulate tyrosine and serine-threonine substrate phosphorylations. One substrate (p68) is phosphorylated by many CSF stimulants, including IL-2, suggesting a highly conserved role in many unique receptor(s) signal transduction processes. The proliferative CSFs and IL-2 also stimulate the expression of many of the same genes including proto-oncogenes,
ornithine decarboxylase
and members of the ancient family of stress response genes. Although initial membrane events may differ among the respective proliferative stimulants, biochemical and molecular convergence on highly conserved cellular substrates and the programme of gene expression is seen.
...
PMID:Molecular events associated with the action of haemopoietic growth factors. 327 Apr 54