The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulat- in...The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulat- ing Wnt signaling： on one hand, Axin scaffolds the ＂l^-catenin destruction complex＂ to promote 13-catenin degradation and therefore inhibits the Wnt signal transduction; on the other hand, Axin interacts with LRP5/6 and facilitates the recruitment of GSK3 to the plasma membrane to promote LRP516 phosphorylation and Wnt signaling. The differential assemblies of Axin with these two distinct complexes have to be tightly controlled for appropriate transduction of the ＂on＂ or ＂off＂ Wnt signal. So far, there are multiple mechanisms revealed in the regulation of Axin activity, such as post- transcriptional modulation, homo/hetero-polymerization and auto-inhibition. These mechanisms may work cooperatively to modulate the function of Axin, thereby playing an important role in controlling the canonical Wnt signaling. In this review, we will focus on the recent progresses regarding the regulation of Axin function in canonical Wnt signaling.展开更多
The ROP1 GTPase-based signaling network controls tip growth in Arabidopsis pollen tubes. Our previous studies imply that ROP1 might be directly activated by RopGEF1, which belongs to a plant-specific family of Rho gua...The ROP1 GTPase-based signaling network controls tip growth in Arabidopsis pollen tubes. Our previous studies imply that ROP1 might be directly activated by RopGEF1, which belongs to a plant-specific family of Rho guanine nucleotide exchange factors （RopGEFs） and in turn may be activated by an unknown factor through releasing RopGEFI＇s auto-inhibition. In this study, we found that RopGEF1 forms a complex with ROP1 and AtPRK2, a receptor-like protein kinase previously shown to interact with RopGEFs. AtPRK2 phosphorylated RopGEF1 in vitro and the atprkl,2,5 tri- ple mutant showed defective pollen tube growth, similar to the phenotype of the ropgef1,9,12,14 quadruple mutant. Overexpression of a dominant negative form of AtPRK2 （DN-PRK2） inhibited pollen germination in Arabidopsis and reduced pollen elongation in tobacco. The DN-PRK2-induced pollen germination defect was rescued by overexpressing a constitutively active form of RopGEF1, RopGEF1（90-457）, implying that RopGEF1 acts downstream of AtPRK2. Moreover, AtPRK2 increased ROP1 activity at the apical plasma membrane whereas DN-PRK2 reduced ROP1 activity. Finally, two mutations at the C-terminal putative phosphorylation sites of RopGEF1 （RopGEF1S460A and RopGEF1S480A） eliminated the function of RopGEF1 in vivo. Taken together, our results support the hypothesis that AtPRK2 acts as a positive regula- tor of the ROP1 signaling pathway most likely by activating RopGEF1 through phosphorylation.展开更多
文摘The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulat- ing Wnt signaling： on one hand, Axin scaffolds the ＂l^-catenin destruction complex＂ to promote 13-catenin degradation and therefore inhibits the Wnt signal transduction; on the other hand, Axin interacts with LRP5/6 and facilitates the recruitment of GSK3 to the plasma membrane to promote LRP516 phosphorylation and Wnt signaling. The differential assemblies of Axin with these two distinct complexes have to be tightly controlled for appropriate transduction of the ＂on＂ or ＂off＂ Wnt signal. So far, there are multiple mechanisms revealed in the regulation of Axin activity, such as post- transcriptional modulation, homo/hetero-polymerization and auto-inhibition. These mechanisms may work cooperatively to modulate the function of Axin, thereby playing an important role in controlling the canonical Wnt signaling. In this review, we will focus on the recent progresses regarding the regulation of Axin function in canonical Wnt signaling.
基金a MOST 973 project，National Institute of General Medical Research，DOE (DE-FG02-04ER15555,which supported F.C.and the biochemical experiments described in this work) to Z.Y.,and a National Science Foundation of China (31070274) to F.C
文摘The ROP1 GTPase-based signaling network controls tip growth in Arabidopsis pollen tubes. Our previous studies imply that ROP1 might be directly activated by RopGEF1, which belongs to a plant-specific family of Rho guanine nucleotide exchange factors （RopGEFs） and in turn may be activated by an unknown factor through releasing RopGEFI＇s auto-inhibition. In this study, we found that RopGEF1 forms a complex with ROP1 and AtPRK2, a receptor-like protein kinase previously shown to interact with RopGEFs. AtPRK2 phosphorylated RopGEF1 in vitro and the atprkl,2,5 tri- ple mutant showed defective pollen tube growth, similar to the phenotype of the ropgef1,9,12,14 quadruple mutant. Overexpression of a dominant negative form of AtPRK2 （DN-PRK2） inhibited pollen germination in Arabidopsis and reduced pollen elongation in tobacco. The DN-PRK2-induced pollen germination defect was rescued by overexpressing a constitutively active form of RopGEF1, RopGEF1（90-457）, implying that RopGEF1 acts downstream of AtPRK2. Moreover, AtPRK2 increased ROP1 activity at the apical plasma membrane whereas DN-PRK2 reduced ROP1 activity. Finally, two mutations at the C-terminal putative phosphorylation sites of RopGEF1 （RopGEF1S460A and RopGEF1S480A） eliminated the function of RopGEF1 in vivo. Taken together, our results support the hypothesis that AtPRK2 acts as a positive regula- tor of the ROP1 signaling pathway most likely by activating RopGEF1 through phosphorylation.
