Recombinant Mouse Wnt-5b Protein

Wnt proteins are cysteine-rich secreted glycoproteins that play critical roles in both carcinogenesis and embryonic development. Wnts bind to receptors of the Frizzled family in conjunction with a coreceptor of the low-density lipoprotein receptor-related protein family (LRP-5 or -6), or the Ryk atypical receptor tyrosine kinase (1-3). Downstream effects of Wnt signaling occur through multiple pathways with differing intracellular components: the canonical Wnt/ beta-catenin pathway, the Wnt/Ca²⁺ pathway, and the planar cell polarity (PCP) pathway (1-4). Wnt-5b is a 49 kDa glycoprotein that is implicated in the Wnt/Ca²⁺ and PCP pathways (4‑8). These pathways can inhibit canonical Wnt/ beta-catenin signaling (4, 7). Human and mouse Wnt-5b are synthesized as 359 amino acid (aa) precursors that contain a 17 aa signal sequence and a 342 aa mature region. Mature mouse Wnt-5b shares 94%, 98%, 90% and 88% aa identity with mature human, rat, chick and Xenopus Wnt-5b, respectively. Although Wnt-5a and Wnt-5b share 83% aa identity, their effects may be different. For example, Wnt-5b, but not Wnt-5a, promotes cell cycle progression and is weakly transforming (8, 9). Wnt-5a and -5b are thought to coordinate developmental events, such as chondrocyte differentiation and formation of endochondral bone (5, 6, 10). In contrast to more focused expression of Wnt-5a, Wnt-5b is constitutively expressed at low levels throughout mouse embryonic development (10, 11). In adult mice, Wnt-5b is widely expressed, including heart, liver, brain, lung, testes, kidney, and pancreas (11-13). Wnt-5b is up‑regulated during early adipogenesis, and its overexpression in 3T3-L1 cells partially inhibits canonical Wnt suppression of adipogenesis (7, 14). It enhances PPAR gamma expression and promotes differentiation of preadipocytes (14). Human Wnt-5b polymorphisms have been associated with Type II diabetes (12).