GSK-3β

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Introductions

GSK-3β is an evolutionarily very conserved serine/threonine kinase. It is ubiquitous in mammalian eukaryotic cells, and in addition to regulating glycogen synthase (GS) activity, which was first identified, GSK-3β also acts on numerous signaling structural proteins and transcription factors to regulate cell differentiation, proliferation, survival and apoptosis. Its selection as a therapeutic target has received increasing attention from researchers in the study of various major diseases such as cancer neurodegenerative diseases neuropsychiatric disorders.

Figure 1. Structure of GSK-3β.

Biological Properties of GSK-3β

GSK-3 was first isolated from fractionated extracts of rabbit skeletal muscle, and there are two main isoforms, GSK-3α and GSK-3β, which share 98% homology in the catalytic region and differ slightly in the N- and C-termini. GSK-3β is a key enzyme involved in hepatic glucose metabolism, which inhibits its activity by phosphorylating GS, decreases hepatic glucose synthesis and increases blood glucose concentration in vivo, and is controlled by insulin in the insulin signaling pathway to participate in hepatic glucose anabolism. Meanwhile, GSK-3β also regulates the ratio of Bax/HKII by affecting the concentration of glucose in blood, which in turn affects mitochondrial permeability and cytochrome C release, and participates in the regulation of apoptosis.

Inhibition of GSK3

Phosphorylation of a serine at the amino terminus of GSK3 (Ser9 of GSK-3Β or Ser21 of GSK3a) significantly inhibits its activity. kinases of several signaling pathways such as Akt, protein kinase A (PKA), protein kinase C(PKC) and P90R s k can phosphorylate this site. There are also other substances that inhibit this site.

Activation of GSK3

In contrast to the activity-inhibiting effect of serine site phosphorylation, phosphorylation of tyrosine sites of GSK3 (Tyr216 of GSK3β, Tyr279 of GSK3α) promotes its activity. Most substrates of GSK3 need to be phosphorylated at a serine or threonine site by other protein kinases first. This phosphorylated serine or threonine residue, called the initiating phosphate, is located four residues from the GSK3 phosphorylation site at the carboxy terminus of the substrate protein, and binds to GSK3 in order to enable the latter to function.

Functions of GSK-3β

GSK-3β is involved in the regulation of glucose metabolism, cell signaling, cell proliferation, growth, migration, differentiation, cell cycle, embryonic development, apoptosis, insulin response and various transcription factors to regulate organ growth and death. GSK-3β plays a role in many diseases such as diabetes, Alzheimer's disease, inflammation, cancer, etc. GSK-3β is regulated is has a dual role. For example, GSK-3Β inhibits androgen receptor-stimulated cell growth in prostate cancer, and thus behaves as a cancer suppressor. In contrast, GSK-3β is highly para-expressed in colon cancer, and GSK-3β plays a facilitating role in NF-kB-regulated pancreatic cancer cell survival.

GSK-3β Antibodies

GSK-3β antibodies were systemically immunized with GSK-3β in rabbits then rabbit GSK-3β-sensitized B cells were screened and then crossed with bone marrow tumor cells to finally produce a GSK-3β antibody hybrid cell line that both produces a single GSK-3β antibody and can proliferate indefinitely. Glycogen synthase kinase 3, also known as GSK3B, is an enzyme that in humans is encoded by the gene encoding GSK-3β. In mice, the enzyme is encoded by the GSK-3β gene. aberrant regulation and expression of GSK3β is associated with increased susceptibility to bipolar affective disorder. Glycogen synthase kinase-3 (GSK-3) is a proline-directed serine-threonine kinase that was originally identified as a phosphorylating and inactivating agent of glycogen synthase.