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Details on Person RYK is an atypical receptor tyrosine kinase-like receptor th...
| Class:Id | Summation:5323533 |
|---|---|
| _displayName | RYK is an atypical receptor tyrosine kinase-like receptor th... |
| _timestamp | 2014-02-18 15:22:48 |
| created | [InstanceEdit:5323532] Rothfels, K, 2014-02-15 |
| modified | [InstanceEdit:5333041] Rothfels, K, 2014-02-18 [InstanceEdit:5333042] Rothfels, K, 2014-02-18 |
| text | 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 and signaling through RYK is believed to contribute to both canonical and non-canonical WNT pathways (Lu et al, 2004; Keeble et al, 2006b; Liu et al, 2005; Macheda et al, 2012; Schmitt et al, 2006; reviewed in Keeble et al, 2006a). Expression of a beta-catenin-dependent reporter gene has been demonstrated after RYK-binding by WNT1 and WNT3A, however the details of downstream signaling remain to be clarified (Lu et al, 2004; Berndt et al, 2011). Signaling through RYK may occur in the context of a RYK-FZD co-receptor and appears to involve the recruitment of DVL (Lu et al, 2004). The E3 ligase Mindbomb (MIB1) was also identified as a RYK-interacting protein that contributes to canonical WNT signaling, possibly by regulating the levels of RYK at the cell surface (Berndt et al, 2011). Finally, RYK has been shown to be cleaved by gamma-secretase in response to WNT3, liberating a intracellular domain (ICD) that translocates to the nucleus and that is required for neuronal differentitation (Lyu et al, 2008). The significance of these findings is not yet fully clear. |
| (summation) | [Reaction:5323545] Canonical WNT signaling through the atypical receptor RYK [Homo sapiens] |
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