Wnt5A belongs to the Wnt family of secreted glycoproteins with a conserved pattern of cysteine residues (22–24). Wnt proteins are subdivided into two functional classes on the basis of their different biological effects. Members of the Wnt1/Wingless class transform C57MG cells and induce secondary axis formation in Xenopus. This effect is based on activation of the Wnt–β-catenin pathway, which involves the stabilization of cytoplasmic β-catenin and transcriptional regulation through the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors. Members of the Wnt5A class fail in both assays and activate non-canonical Wnt pathways. These involve different kinases such as protein kinase C (PKC), calmodulin-dependent protein kinase II (CamKII) and c-Jun N-terminal kinase (JNK), as well as phosphatases such as calcineurin (CaCN). Members of the Rho class of GTPases such as Rho, Rac and Cdc42 are regulated by non-canonical Wnt signaling as well. This pathway resembles the planar cell polarity pathway in Drosophila. Non-canonical Wnt pathways inhibit the canonical Wnt–β-catenin pathway. The specificity of Wnt signaling depends on the interaction of Wnts with its receptors of the Frizzled and low-density lipoprotein receptor-related protein (LRP) families as well as co-receptors of the Ror and Ryk families. Wnt5A has been shown to regulate cell movements during gastrulation in fish and frogs. Wnt5A has also some influence on dorsoventral patterning as shown in fish that are mutant for Wnt5A. Furthermore, Wnt5A has been implicated as a tumor suppressor gene. Additionally, a role for Wnt5A in metastasis has been reported. Treatment of primary midbrain precursor cells with purified Wnt5A induced differentiation into dopaminergic, tyrosine hydroxylase-positive neurons.
Alternative names for this molecule:
hWNT5A; Wingless-related MMTV integration site 5A; Wingless-type MMTV integration site family, member 5A; Wnt-5a; Wnt5a