Abstract
Insulin signaling is mediated by a cascade of phosphorylation/dephosphory-lation reactions via the stimulation of specific serine/threonine (ser/thr) kinases and phosphatases (1–7). Dephosphorylations catalyzed by ser/thr phosphatases result in the activation or inhibition of several intracellular enzymes and proteins that govern the final steps of insulin action (2). The best examples are glycogen synthase (GS), pyruvate dehydrogenase (PDH), acetyl-CoA carboxylase, hormone-sensitive lipoprotein lipase, and Glut-4 (the insulin regulatable muscle/fat glucose transporter) (1–10). Dephosphorylation increases the activity of GS, PDH, and Glut-4, and inhibits phosphorylase kinase (2,8–10). Protein phosphatase 1 (PP1) appears to be the key enzyme responsible for connecting the insulin-initiated phosphorylation cascade with the dephosphorylation of insulin-sensitive substrates (2). The exact in vivo molecular mechanism by which insulin regulates the activity of this enzyme remains unclear. A large proportion of the spontaneously active PP1 is found associated with the particulate fraction of the cell, notably with glycogen, membranes, and myofibrils (11). Therefore, it appears that the catalytic activity of PP1 is determined by its interaction with regulatory subunits that target the enzyme to particular locations in the cell and alter its substrate specificity (11).
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Ragolia, L., Begum, N. (1998). The Relationship Between Insulin Signaling and Protein Phosphatase 1 Activation. In: Ludlow, J.W. (eds) Protein Phosphatase Protocols. Methods in Molecular Biology™, vol 93. Humana Press. https://doi.org/10.1385/0-89603-468-2:157
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DOI: https://doi.org/10.1385/0-89603-468-2:157
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