To identify novel regulators of Wnt signaling, we performed yeast two-hybrid analyses with Dvl-1 and identified BP75 as a candidate. Here, we demonstrated that BP75 directly interacts with Dvl-1 in mammalian cells and enhances TCF-dependent gene expression induced by Dvl-1. In support of these results, BP75 in cooperation with Dvl-1 was found to facilitate dephosphorylation at Tyr216 of glycoge...

Muscle extracts were subjected to fractionation with ethanol, chromatography on DEAE-cellulose, precipitation with (NH4)2SO4 and gel filtration on Sephadex G-200. These fractions were assayed for protein phosphatase activities by using the following seven phosphoprotein substrates: phosphorylase a, glycogen synthase b1, glycogen synthase b2, phosphorylase kinase (phosphorylated in either the al...

The hormonal regulation of glycogen synthase has been studied with isolated perfused hearts that were depleted of 85% of their endogenous glycogen. Glycogen depletion alone promoted a 3-fold activation of glycogen synthase and magnified by 3-fold the response to insulin. Glycogen depletion also facilitated the detection of epinephrine-promoted glycogen synthase inactivation. Hormonal effects on...

Phellodendrine is a Phellodendri Cortex-derived isoquinoline alkaloids, has been shown to have various activities, especially hypoglycemic effect in mice, predicting its medicinal value on diabetes mellitus. To further understand the pharmacological of phellodendrine mellitus, network techniques used elaborate involved mechanisms. 84 common target molecules were screened, based chemical structu...

While deficient brain plasticity is a well-established pathophysiologic feature of depression, little is known about disorder-associated enhanced cognitive processing. Here, we studied a novel mouse paradigm that potentially models augmented learning of adverse memories during development of a depressive-like state. We used a modification of the classic two-day protocol of a mouse Porsolt test ...

We have developed a general method of making conditional alleles that allows the rapid and reversible regulation of specific proteins. A mouse line was produced in which proteins encoded by the endogenous glycogen synthase kinase-3 beta (GSK-3beta) gene are fused to an 89 amino acid tag, FRB*. FRB* causes the destabilization of GSK-3beta, producing a severe loss-of-function allele. In the prese...

To study the effects of phosphorylation by glycogen synthase kinase-3beta (GSK-3beta) on the ability of the microtubule-associated protein tau to promote microtubule self-assembly, tau isoform 1 (foetal tau) and three mutant forms of this tau isoform were investigated. The three mutant forms of tau had the following serine residues, known to be phosphorylated by GSK-3, replaced with alanine res...

Beta-catenin can be cleaved by caspase-3 or degraded by activated glycogen synthase kinase-3beta via phosphorylating beta-catenin. We tested the hypothesis that beta-catenin undergoes degradation after stroke, and its degradation is dependent on caspase activity. Stroke was generated by permanent middle cerebral artery occlusion and 1 h of transient bilateral common carotid artery occlusion in ...