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#GSK-3

3 public questions tagged with this topic.

Blocking GSK-3 in sea urchin embryos leads to:

GSK-three normally phosphorylates beta-catenin within destruction complex containing Axin and APC, marking it for degradation by beta-TrCP ubiquitin ligase and proteasome. Vegetal Dishevelled inhibits GSK-three locally, allowing beta-catenin accumulation in micromeres and macromeres vegetally. Chemical inhibition of GSK-three with lithium chloride or genetic dominant negative constructs eliminates degradation globally in all blastomeres. Consequently beta-catenin accumulates in all nuclei including animal pole cells that normally remain ectodermal. Animal blastomeres then ectopically activate

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 10: GSK-3 block causes beta-catenin accumulation all nuclei vegetalization.

GSK-3 normally functions by:

In resting cells GSK-3 beta resides in destruction complex with scaffold Axin and tumor suppressor APC, phosphorylating N-terminal residues Ser33, Ser37, Thr41 of beta-catenin. Phosphorylated beta-catenin recognized by beta-TrCP E3 ubiquitin ligase leading to ubiquitination and proteasomal degradation, keeping cytoplasmic levels low. Wnt signaling displaces complex via Dishevelled and GBP inhibiting GSK-3, preventing phosphorylation. Thus GSK-3 normally functions by degrading beta-catenin ventrally. Dorsal Wnt11 signaling inhibits GSK-3 allowing beta-catenin accumulation, nuclear translocation

Ref: NCBI Bookshelf, Molecular Biology of the Cell, Chapter 19: GSK-3 function - beta-catenin degradation in Wnt pathway.

GSK-3 negatively regulates:

Glycogen synthase, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)