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Inhibit GSK-3β or there’s heartbreak dead ahead
Elizabeth Murphy
Elizabeth Murphy
Published June 1, 2004
Citation Information: J Clin Invest. 2004;113(11):1526-1528. https://doi.org/10.1172/JCI21986.
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Commentary

Inhibit GSK-3β or there’s heartbreak dead ahead

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Abstract

Numerous signaling pathways have been shown to mediate cardioprotection, but the end effectors that mediate protection are only beginning to be elucidated. Numerous cardioprotective drugs are shown to converge on glycogen synthase kinase-3β (GSK-3β) . The phosphorylation and inhibition of GSK-3β lead to inhibition or delayed activation of the mitochondrial permeability transition, a key regulator of apoptosis.

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Elizabeth Murphy

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Figure 1

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GSK-3β is phosphorylated and inhibited by a number of kinases. In the ab...
GSK-3β is phosphorylated and inhibited by a number of kinases. In the absence of upstream kinases, unphosphorylated GSK-3β is active, and it phosphorylates and inactivates downstream targets such as glycogen synthase to modulate metabolism or phosphorylates transcription factors and targets them for degradation. Juhaszova et al. (9) suggest that phosphorylation and inactivation of GSK-3β also reduce activity of the MPT. Most GSK-3β substrates are phosphorylated by another kinase prior to phosphorylation by GSK-3β (12). GS, glycogen synthase; p70s6k, p70 ribosomal S6 kinase; RSK, p90 ribosomal S6 kinase; ILK, integrin-linked kinase; WNT, homologues of Wingless; P, phosphorylation.

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