Recombinant Mouse Ryk Fc Chimera Protein, CF

Ryk (Related to tyrosine kinase), also called VIK in mouse, is an 70‑90 kDa type I transmembrane glycoprotein that is an atypical member of the receptor tyrosine kinase superfamily (1, 2). Mouse Ryk cDNA encodes 594 amino acids (aa) that include a 34 aa signal sequence, a 177 aa extracellular domain (ECD) that contains a WIF (Wnt Inhibitory Factor) domain (aa 50‑178), a transmembrane sequence, and a cytoplasmic region with a non‑functional Ser/Thr protein kinase domain (aa 317‑590) (1‑3). The cytoplasmic region participates in signaling by undergoing gamma‑secretase cleavage and translocating to the nucleus in response to Wnts (4). Alternate start sites at aa 28 or aa 117 have been reported. Within the ECD, mouse Ryk shares 94% and 100% aa sequence identity with mouse and rat Ryk, respectively. Ryk protein expression is reported in developing neurons of the corticospinal tract, ventral zone, and retina, as well as adult tissue epithelia, stroma and blood vessels (4‑9). Ryk binds Wnts and EphB2/B3 receptors via its WIF domain (8‑10). It may form a Wnt receptor complex with Frizzled receptors, serving as a link between Wnt and Dishevelled and converting Wnt/Frizzled attraction signals to repulsion signals (6‑8, 10). In particular, Ryk is required for Wnt5a‑induced axon guidance after cortical axons cross the corpus callosum, and for Wnt3‑mediated guidance of developing retinal ganglion cells (7, 8). Mice deleted for the Ryk gene show defects in axon guidance that produce craniofacial defects and shortened limbs (10, 11). Ryk^-/- mice share a cleft palate phenotype with EphB2/B3‑deleted mice (10). Ryk is often over‑expressed in human ovarian cancer (5).