R-spondin-2

Definition:

Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form.

References:

[1]. Wim de Lau, et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature. 2011 Jul 4;476(7360):293-7. [Content Brief]

[2]. Xing Gong, et al. LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor. PLoS One. 2012;7(5):e37137. [Content Brief]

[3]. Andrei Glinka, et al. LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling. EMBO Rep. 2011 Sep 30;12(10):1055-61. [Content Brief]

[4]. Emmanuelle Szenker-Ravi, et al. RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6. Nature. 2018 May;557(7706):564-569. [Content Brief]

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