Is glycogen synthase kinase-3[beta] an ultraconserved kernel enzyme?

• Published in: Gene expression to genetical genomics Vol. 2; p. 1
• Main Authors: Fenger M, Haugaard, S.B, Andersen, O, Madsbad, S, Werge, T, Linneberg, A
• Format: Journal Article
• Language: English
• Published: London Sage Publications Ltd. (UK) 11.12.2009; Sage Publications Ltd
• Subjects: Diabetes; Glycogen; Phosphotransferases; Physiological aspects; Risk factors; Synthesis; Denmark
• ISSN: 1179-5697; 1179-5697

Glycogen synthase kinase 3 P (GSK3[beta]) was discovered as a major factor in glucose homeostasis. GSK3[beta] is a pivotal regulator of glycogen synthesis by altering the activity of glycogen synthase and perturbation in this process have been linked to at least some sub-entities of insulin resistance and diabetes mellitus. However, GSK3[beta] has a central role in many biochemical and physiological processes apparently not related to insulin resistance or diabetes. The functionality of GSK3[beta] is vast including more than 33 substrates and 72 protein-protein interactions, and is involved in such diverse diseases as cancer, schizophrenia, inflamation, cardiac diseases and many more. Considering this scale of the involvement of GSK3[beta], many related to developmental processes, suggests that either is GSK3[beta] a high-level network-hub or is a peripheral kinase in several non- connected networks. Here, evidence is provided that GSK3 [beta] is an ultraconserved protein which would suggest that the enzyme qualify to be a kernel protein in the sense that life as we know it depends on conserved molecular entities to provide the essential functionality to an organism. The enzyme has evolved under strong purifying selection implicating that GSK3[beta] is a functional hub. Keywords: glycogen synthase kinase 3[beta], insulin resistance, diabetes mellitus