Find FZD1 Products Interaction Network for FZD1 FZD1 Details

Related Pathways Wnt / beta-catenin Signaling Axonal Guidance Signaling View All Pathways

Synonyms: AW227548, DKFZp564G072, Frizzled 1, FZ-1, FZD1, Rfz1

Wnt Signaling

The Wnt (wingless) signaling network regulates diverse processes during development such as cell fate determination, structural remodeling, cell polarity and morphology, cell adhesion, and growth. The network is composed of secreted glycoproteins, Wnt family ligands, and the Frizzled and low-density lipoprotein (LDL) receptor-related protein LRP (LRP5/6, Arrow) families of receptors. The Frizzled receptor is involved with two distinct signaling pathways referred to as the canonical and non-canonical pathways. The canonical pathway involves the regulation of beta-catenin (Armadillo) stabilization and gene expression. The non-canonical pathway refers to a signaling pathway that regulates planar cell polarization (PCP), a process that establishes the uniform alignment of structures in the epithelium.

Beta-catenin (β-catenin) mediates a number of physiological effects that are dependent in-part on its cell level and location. Normal levels of beta-catenin associate with cadherins to promote cell adhesion and to control cell shape in association with the microfilament cytoskeletal network. Normal levels of cytoplasmic β-catenin are maintained by a regulated process that directs the degradation of excess β-catenin. Beta-catenin degradation is regulated by a series of phosphorylations that involve cyclin-CDK2 in association with cyclin A or E and GSK3beta. CDK2:cyclin primes beta-catenin for phosphorylation by GSK3beta. In the cytoplasm, GSK3beta and beta-catenin are associated with a destruction complex that also contains Axin and adenomatous polyposis coli (APC). Beta-catenin phosphorylated by GSK3 is bound by the beta-TrCP component of the ubiquitin ligase complex and degraded. GSK3 is constitutively active and must be inhibited to prevent the degradation of beta-catenin. Wnt signaling through the Frizzled and LRP receptor pair activates Dishevelled (Dvl) and inhibits GSK3beta. Consequently when wnt signaling is active the level of beta-catenin becomes elevated and it enters the nucleus where it interacts with gene regulators such as T-cell factor (TCF)/lymphoid enhancer factor (LEF) to mediate gene expression.