Recombinant Human 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 human Wnt‑5b shares 95%, 94%  90%, 89% and 86% aa identity with mature mouse, rat, bovine, 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).