Phosphorylation of LRP5/6 cytoplasmic domain by membrane-associated GSK3beta

LRP5/6 contains 5 PPP(S/T)PxS motifs in its intracellular domain which have been shown to be phosphorylated by a membrane-associated pool of GSK3beta. Individual phosphorylation of each of these motifs promotes interaction with AXIN and stimulates WNT signaling as assessed by activation of a TCF/beta-catenin responsive reporter (Tamai et al, 2004; Zeng et al, 2005; MacDonald et al, 2008). In the context of full length LRP6, phosphorylation of the five motifs shows cooperative stimulation of AXIN binding and WNT signaling. GSK3beta-mediated phosphorylation of LRP6 is thought to prime the receptor for subsequent phosphorylation by CSNK1 (Zeng et al, 2005; reviewed in He et al, 2004).

LRP5/6 在其细胞内结构域中包含5个PPP(S/T)PxS基序，这些基序已被证实可以被与膜结合的GSK3beta磷酸化。每个基序的单独磷酸化均能促进与AXIN的结合并刺激WNT信号通路，这一作用通过激活TCF/β-catenin响应的报道基因得以评估（Tamai等，2004；Zeng等，2005；MacDonald等，2008）。在全长LRP6的背景下，五个基序的磷酸化表现出对AXIN结合和WNT信号通路的协同刺激作用。LRP6的GSK3beta介导的磷酸化被认为是为后续由CSNK1引起的磷酸化做好了受体准备（Zeng等，2005；参见He等，2004年的综述）。