Fz2

Fz2, or Frizzled-2 (FZD2), is a member of the Frizzled family of seven-pass transmembrane receptors that mediate Wnt signaling. It functions as a cell surface receptor for Wnt ligands and participates in both canonical (beta-catenin–dependent) and noncanonical signaling pathways, depending on cellular context and available co-receptors.

The receptor's extracellular region contains a cysteine-rich domain responsible for binding Wnt proteins, while its intracellular tail includes motifs that interact with cytoplasmic signaling partners, notably Dishevelled. This interaction links Wnt binding to downstream signaling cascades. In canonical signaling, Fz2 cooperates with LRP5/6 co-receptors to inhibit the beta-catenin destruction complex, allowing beta-catenin to accumulate and enter the nucleus to regulate target gene transcription. In noncanonical pathways, Fz2 can influence cytoskeletal dynamics and cell polarity through Rho family GTPases, JNK activation, or calcium signaling, with outcomes that affect cell movement and organization.

Fz2 is expressed in multiple tissues and during embryonic development, where it contributes to processes such as neural patterning, cell proliferation, migration, and tissue organization. Its activity often intersects with other signaling pathways, including Notch and BMP, reflecting the integrated nature of developmental signaling networks.

Genetic and functional studies, including knockout models and receptor modulator research, indicate that Fz2 participates in normal development and tissue homeostasis, and that dysregulation of Frizzled signaling can contribute to disease. Because of its central role in Wnt signaling, Fz2 is a focus in studies of cancer biology and regenerative medicine, where selective modulation of Frizzled receptors holds therapeutic potential.