Wnt5a, a member of the highly conserved Wnt protein family, is a 352 amino acid protein containing 23 conserved cysteines and contains a cysteine modified by palmitate which is essential for receptor binding and biological activity. The Wnt5a amino acid sequence also contains an N-terminal signal peptide which means the protein is secreted into the medium when expressed in cell culture. Wnt ligands bind to cell surface co-receptors consisting of a Frizzled protein and lipoprotein receptor related protein (5/6). Wnt 5a belongs to the non-canonical class of Wnt proteins which are independent of or inhibit beta-catenin signalling. Wnt5a when bound to its receptor triggers an intracellular Ca release which activates PKC and CaMK11 which in turn activates TAK1 MAPkinase-kinase and nemo-like(NLK) kinase. NLK phosphorylates Lef1/TCF protein complex inhibiting the formation of the beta-catenin Lef1/TCF DNA complex. In contrast Wnt3a signalling stabilizes beta-catenin increasing the formation of the beta-catenin Lef1/TCF DNA complex. Wnt signalling has been implicated in the control of differentiation of stem cells. The Wnts have also been shown to have putative roles in the regulation of adult stem cells. Recently injection of embryonic stem cells into hearts has been shown to correct cardiac defects. This occurs through the secretion of factors from stem cells which correct gene defects in neighbouring cells. Wnt5a, a short term factor secreted by the stem cells, has been shown to be critical for this process (Fraidenraich and Benzra, 2006).
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