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).
Shi, J, Schmitt, AM, Zou, Y, Lu, CC, Wolf, AM, King, LA
Seaman, C, Halford, MM, Anderson, RB, Stacker, SA, Keeble, TR, Macheda, M, Kee, N, Cooper, HM
Zhang, X, Yang, Y, Halford, MM, Stacker, SA, Gao, B, Wang, Q, Wang, N, Andre, P, Schilit, A
Lieschke, GJ, Kugathasan, K, Halford, MM, Sun, WW, Zhang, YF, Stacker, SA, Jacques, BE, Bower, NI, Hogan, BM, Dabdoub, A, Macheda, ML
Shi, J, Zou, Y, Lu, CC, Song, XJ, Liu, Y, Lyuksyutova, AI, Wang, ZB
Fradkin, LG, Noordermeer, JN, Dura, JM
Keeble, TR, Cooper, HM
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