Pharmacological inhibition of GSK-3 is not strictly correlated with a decrease in tyrosine phosphorylation of residues 216/279

• Published in: Journal of neuroscience research 2008-02, Vol.86 (3), p.668-674
• Main Authors: Simón, D., Benitez, M. J., Gimenez-Cassina, A., Garrido, J. J., Bhat, R. V., Díaz-Nido, J., Wandosell, F.
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Enzyme Inhibitors - pharmacology; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 - chemistry; Glycogen Synthase Kinase 3 - metabolism; GSK-3 inhibition; Lysophospholipids - pharmacology; Mice; neuronal cells; Peptide Fragments - metabolism; Phosphorylation - drug effects; Protein Kinase Inhibitors - pharmacology; Protein Tyrosine Phosphatases - antagonists & inhibitors; Tyrosine - metabolism; tyrosine kinase inhibition; tyrosine phosphatase inhibition; Vanadates - pharmacology
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21523

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. © 2007 Wiley‐Liss, Inc.