RYK binds WNT5A and VANGL2

Stable Identifier
Reaction [binding]
Homo sapiens
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RYK is an atypical receptor tyrosine kinase-like receptor that is required for craniofacial and skeletal development, axon guidance and neuronal differentiation. RYK has an extracellular WNT-binding WIF domain, a putative tetrabasic cleavage site, an intracellular PDZ domain and a cytosolic RTK-like catalytic site that is rendered inactive by a number of substitutions at conserved positions (reviewed in Fradkin et al, 2010; Keeble et al, 2006a). The WIF domain of RYK has been shown to interact with WNT1, 3, 3A and 5A (Keeble et al, 2006b; Liu et al, 2005; Macheda et al, 2012; Schmitt et al, 2006). RYK-deficient mice show disruptions to cochlear hair cell orientation suggesting a role for RYK in the planar cell polarity (PCP) pathway. Consistent with this, RYK binds to the PCP protein VANGL2 as assessed by co-immunoprecipitation from HEK293 cells. Formation of a RYK:VANGL2 complex appears to stabilize VANGL2 protein levels through an unknown mechanism (Macheda et al, 2012; Andre et al, 2012). RYK:VANGL may activate RHO A in response to WNT signaling (Macheda et al, 2012).

Literature References
PubMed ID Title Journal Year
16280981 Wnt-Ryk signalling mediates medial-lateral retinotectal topographic mapping

Shi, J, Schmitt, AM, Zou, Y, Lu, CC, Wolf, AM, King, LA

Nature 2006
16723543 The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum

Seaman, C, Halford, MM, Anderson, RB, Stacker, SA, Keeble, TR, Macheda, M, Kee, N, Cooper, HM

J. Neurosci. 2006
23144463 The Wnt coreceptor Ryk regulates Wnt/planar cell polarity by modulating the degradation of the core planar cell polarity component Vangl2

Zhang, X, Yang, Y, Halford, MM, Stacker, SA, Gao, B, Wang, Q, Wang, N, Andre, P, Schilit, A

J. Biol. Chem. 2012
22773843 The Wnt receptor Ryk plays a role in mammalian planar cell polarity signaling

Lieschke, GJ, Kugathasan, K, Halford, MM, Sun, WW, Zhang, YF, Stacker, SA, Jacques, BE, Bower, NI, Hogan, BM, Dabdoub, A, Macheda, ML

J. Biol. Chem. 2012
16116452 Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract

Shi, J, Zou, Y, Lu, CC, Song, XJ, Liu, Y, Lyuksyutova, AI, Wang, ZB

Nat. Neurosci. 2005
20004982 Ryks: new partners for Wnts in the developing and regenerating nervous system

Fradkin, LG, Noordermeer, JN, Dura, JM

Trends Neurosci. 2010
16971168 Ryk: a novel Wnt receptor regulating axon pathfinding

Keeble, TR, Cooper, HM

Int. J. Biochem. Cell Biol. 2006
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