Pharmacological inhibition of GSK-3 is not strictly correlated with a decrease in tyrosine phosphorylation of residues 216/279.
Recent evidence suggests that intramolecular autophosphorylation is responsible for the tyrosine phosphorylation (pY) of residues 279 or 216 of glycogen synthase kinase-3 (GSK-3alpha or beta), 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.
Simón
D
D
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) y Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Universidad Autónoma de Madrid, Madrid, Spain.
Benitez
M J
MJ
Gimenez-Cassina
A
A
Garrido
J J
JJ
Bhat
R V
RV
Díaz-Nido
J
J
Wandosell
F
F
D000818:Animals; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D014638:Vanadates; D014443:Tyrosine; D038362:Glycogen Synthase Kinase 3; D017027:Protein Tyrosine Phosphatases; C032881:lysophosphatidic acid