WNT signaling is an evolutionarily conserved pathway involved in many developmental processes like organogenesis, cell differentiation, and determining cell polarity. WNT is a glycoprotein that binds to a family of receptors called Frizzled that initiate several different signaling cascades, many of which involve the protein Disheveled (Dsh). In the canonical WNT pathway, activation of Frizzled results in phosphorylation of Dsh, which inhibits a complex containing APC, Axin and GSK3 from targeting β-catenin (ctnn-β) for proteasomal degradation. This leads to translocation of ctnn-β into the nucleus and expression of various transcription and cellular factors, like c-Myc and p53. Dsh can also signal through Rac1 to trigger JNK activation and cell survival, or through DAAM1/2 and Rho kinase (ROCK) to modulate cell motility. Frizzled binding by WNT5 can initiate signaling of PLC and calcineurin (caln) to activate NFAT, which is involved in regulating cell fates.
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