Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycogen synthase kinase 3 (GSK3) is a widely expressed Ser/Thr protein kinase that phosphorylates numerous substrates. This large number of substrates requires precise and specific regulation of GSK3 activity, which is achieved by a combination of phosphorylation, localization, and interactions with GSK3-binding proteins. Members of the Wnt canonical pathway have been shown to influence GSK3 activity. Through a yeast two-hybrid screen, we identified the Wnt canonical pathway co-receptor protein low density lipoprotein receptor-related protein 6 (LRP6) as a GSK3-binding protein. The interaction between the C terminus of LRP6 and GSK3 was also confirmed by in vitro GST pull-down assays and in situ coimmunoprecipitation assays. In vitro assays using immunoprecipitated proteins demonstrated that the C terminus of LRP6 significantly attenuated the activity of GSK3beta. In situ, LRP6 significantly decreased GSK3beta-mediated phosphorylation of tau at both primed and unprimed sites. Finally, it was also demonstrated that GSK3beta phosphorylates the PPP(S/T)P motifs in the C terminus of LRP6. This is the first identification of a direct interaction between LRP6 and GSK3, which results in an attenuation of GSK3 activity.
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PMID:The low density lipoprotein receptor-related protein 6 interacts with glycogen synthase kinase 3 and attenuates activity. 1636 45

A novel protein from the parasite Trypanosoma cruzi homologous to calcineurin (serine-threonine phosphatase 2B) was identified and characterized. The Calcineurin A gene is present as a single copy gene per haploid genome and encodes a protein of 43 kDa that is expressed in all major developmental stages of T. cruzi. Surprisingly, it is mainly localized in the cell nucleus, in sharp contrast with its mammalian counterpart. The T. cruzi calcineurin A protein presents the three invariants motifs characteristic of the PPP serine-threonine phosphatase superfamily. However, out of the four domains typically present in all calcineurin described to date, the T. cruzi calcineurin A possess only two domains: the catalytic and the calcineurin B binding domain. Sequence similarity searches in the T. cruzi, Trypanosoma brucei and Leishmania major genomes revealed that only L. major presents a gene encoding a putative protein containing the four domains. On the other hand, the T. cruzi Calcineurin B subunit showed a conserved structure, and a reasonable level of similarity over the entire length with calcineurin B proteins from other organisms. Interaction between Calcineurin A and Calcineurin B was analyzed by yeast Two-Hybrid and GST pull-down assays.
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PMID:The Calcineurin A homologue from Trypanosoma cruzi lacks two important regulatory domains. 1720 61