Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We determined the activities of soluble and particulate guanylate cyclase [GTP pyrophosphatelyase (cyclizing); ?EC 4.6.1.2] IN REGENERATING RAT LIVER, FETAL AND NEONATAL RAT LIVER, AND HEPATOMA. TIn these tissues we found increased particulate and decreased soluble enzyme activities compared to normal adult rat liver. The particulate activity increased 12 hr after partial hepatectomy, reached maximal activity at 48 hr, and then declined. The soluble enzyme activity decreased within 8 hr and continued to decline. The activity of homogenates did not change. Guanylate cyclase activity was increased in plasma membrane and microsome fractions from regenerating liver. The increase in particulate activity was prevented with cycloheximide. Decreased soluble and increased particulate enzyme activities were found in fetal liver. After birth the soluble activity increased and the particulate activity decreased. Seven to 14 days after birth the activities of soluble and particulate fractions were similar to those of adult rat liver. In hepatoma 3924A, the activity of particulate guanylate cyclase was 9-fold greater and that of the soluble enzyme was 50% that of normal liver. These studies suggest that guanylate cyclase activity and its subcellular distribution may be related to liver growth through some unknown mechanism.
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PMID:Increased particulate and decreased soluble guanylate cyclase activity in regenerating liver, fetal liver, and hepatoma. 23 4

When supernatants of thymic epithelial cell cultures (STEC) or thymosin fraction 5 were incubated with washed platelets (37 degrees C for 30 min), the levels of platelet guanosine 3',5'-cyclic monophosphate (cyclic GMP) were increased in a dose-dependent manner. In contrast the supernatants from Chang, HeLa, or HCC-M cell cultures did not significantly affect the levels of intracellular cyclic GMP. The increment of intracellular cyclic GMP levels following treatment with STEC increased with longer incubation times until a plateau was reached at 30 min. This activity of STEC was found in fractions with a molecular weight below 10,000 daltons. Contents of guanine and guanosine in STEC were lower than those observed in other culture supernatants. STEC did not affect guanylate cyclase activity in platelets, but significantly inhibited cyclic GMP phosphodiesterase activities in platelet soluble and membrane fractions. Thymosin fraction 5 inhibited the phosphodiesterase activity of the soluble but not the membrane fraction.
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PMID:In vitro effect of thymic epithelial culture supernate on cyclic GMP levels in rabbit platelets. 197 Jun 75

TRIB2 has been identified as an onco-protein, and O-GlcNAcylation of target proteins has been reported to stimulate transformative phenotypes in liver cancer cells. However, the relationships between TRIB2 and O-GlcNAcylation are still unknown. The aim of this study was to investigate whether and how O-GlcNAcylation and TRIB2 regulate each other. We found that stimulation of O-GlcNAcylation elevates TRIB2 by enhancing its protein stability. TRIB2 can be O-GlcNAcylated by the hexosamine biosynthesis pathway (HBP). Also, O-GlcNAcylation boosting of transformative phenotypes of liver cancer cells might occur in a TRIB2-dependent manner. Interestingly, TRIB2 stimulated the metabolism of HBP, demonstrating that TRIB2 has positive feedback on O-GlcNAcylation. Notably, TRIB2 was found to maintain the stability of guanylate cyclase 1 alpha 3 (GUCY1A3), a key component of HBP, by interacting GUCY1A3 and reducing its ubiquitination. Importantly, TRIB2-dependent regulation of metabolism, transformative phenotypes, and O-GlcNAcylation all rely on GUCY1A3. Mouse experiments demonstrate that O-GlcNAcylation of TRIB2 is much higher in the livers of diabetic mice compared to control mice, suggesting that O-GlcNAcylation of TRIB2 might be critical for diabetes-associated liver cancer. Collectively, we have uncovered a positive auto-regulatory feedback between O-GlcNAcylation and TRIB2, which might be regarded as a promising therapeutic target for liver cancer.
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PMID:Reciprocal regulation between O-GlcNAcylation and tribbles pseudokinase 2 (TRIB2) maintains transformative phenotypes in liver cancer cells. 2751 88