Pharmacological inhibition of GSK‐3 is not strictly correlated with a decrease in tyrosine phosphorylation of residues 216/279
- 24 September 2007
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 86 (3), 668-674
- https://doi.org/10.1002/jnr.21523
Abstract
Recent evidence suggests that intramolecular autophosphorylation is responsible for the tyrosine phosphorylation (pY) of residues 279 or 216 of glycogen synthase kinase–3 (GSK-3α or β), an event that appears to play an important role in regulating this kinase. This provocative hypothesis was based on the capacity of certain nonselective GSK-3 inhibitors to alter both the activity of GSK-3 and its pY. Inhibitors of GSK-3 are not always capable of preventing this tyrosine phosphorylation, which may require an extended period of time. For example, although lithium chloride inhibits GSK-3 activity, this inhibition does not alter its pY content. Furthermore, even when GSK-3 activity is impaired, GSK-3 pY can still be modified by physiological or pharmacological agents. Taken together, these data indicate that GSK-3 kinase activity is not necessarily correlated with the extent of GSK-3 pY. We hypothesized that some as-yet-unidentified tyrosine kinases and phosphatases may also regulate this kinase.Keywords
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