• Purity

  >95%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to bind biotinylated recombinant mouse Wnt-3a in a functional ELISA with an estimated K    _D <50 nM.  

• Source

  Chinese Hamster Ovary cell line, CHO-derived

  Human Ryk (Ala46-Thr224) Accession # NP_001005861	IEGRMD	Human IgG1 (Pro100-Lys330)
  N-terminus		C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  Ala46

• Structure / Form

  Disulfide-linked homodimer

• Predicted Molecular Mass

  46.7 kDa (monomer)

• SDS-PAGE

  60-70 kDa, reducing conditions

Background: Ryk

Ryk (Related to tyrosine kinase) is an 70-90 kDa type I transmembrane glycoprotein that is an atypical member of the receptor tyrosine kinase superfamily (1, 2). Human Ryk cDNA encodes 604 amino acids (aa) that include a 25 aa signal sequence, a 199 aa extracellular domain (ECD, aa 26‑224) that contains a WIF (Wnt Inhibitory Factor) domain (aa 63‑191), a transmembrane sequence, and a cytoplasmic region with a nonfunctional Ser/Thr protein kinase domain (aa 327‑600) (1‑3). The cytoplasmic region participates in signaling by undergoing gamma ‑secretase cleavage and translocating to the nucleus in response to Wnts (4). An isoform with a 31 aa substitution between aa 18‑46 is reported. Within the ECD, human Ryk shares approximately 94%, 92%, 86% and 81% aa sequence identity with mouse, rat, equine and canine 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 (1, 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 overexpressed in ovarian cancer (5).

• References:

1. Stacker, S.A. et al. (1993) Oncogene 8:1347.

2. Clark, C.E.J. et al. (2012) Neurosignals 20:202.

3. Katso, R.M. et al. (1999) Mol. Cell. Biol. 19:6427.

4. Lyu, J. et al. (2008) Dev. Cell 15:773.

5. Katso, R.M. et al. (1999) Cancer Res. 59:2265.

6. Liu, Y. et al. (2005) Nat. Neurosci. 8:1151.

7. Schmitt, A.M. et al. (2006) Nature 439:31.

8. Keeble, T.R. et al. (2006) J. Neurosci. 26:5840.

9. Kamitori, K. et al. (2005) Biochem. Biophys. Res. Commun. 330:446.

10. Lu, W. et al. (2004) Cell 119:97.

11. Halford, M.M. et al. (2000) Nat. Genet. 25:414.

• Long Name:

  Receptor Type Tyrosine Protein Kinase RYK

• Entrez Gene IDs:

  6259 (Human); 20187 (Mouse); 140585 (Rat)

• Alternate Names:

  D3S3195; EC 2.7.10; EC 2.7.10.1; hydroxyaryl-protein kinase; JTK5; JTK5A protein tyrosine kinase; JTK5A; RYK receptor-like tyrosine kinase; Ryk; RYK1; tyrosine-protein kinase RYK