Unknown

Dataset Information

0

RhoA GTPase phosphorylated at tyrosine 42 by src kinase binds to ?-catenin and contributes transcriptional regulation of vimentin upon Wnt3A.


ABSTRACT: In the Wnt canonical pathway, Wnt3A has been known to stabilize ?-catenin. In the non-canonical Wnt signaling pathway, Wnt is known to activate Rho GTPases. The correlation between canonical and non-canonical pathways by Wnt signaling, however, has not been well elucidated. Here, we identified that Wnt3A promoted superoxide generation, leading to Tyr42 phosphorylation of RhoA through activations of c-Src and Rho-dependent coiled coil kinase 2 (ROCK2) and phosphorylation of p47phox, a component of NADPH oxidase. Wnt3A also induced accumulation of ?-catenin along with activations of RhoA and ROCK1. Concurrently, ROCK1 was able to phosphorylate GSK-3? at Ser9, which phosphorylated Src at Ser51 and Ser492 residues, leading to Src inactivation through dephosphorylation of Tyr416 during the late period of Wnt3A treatment. Meanwhile, p-Tyr42 RhoA bound to ?-catenin via the N-terminal domain of ?-catenin, thereby leading to the nuclear translocation of p-Tyr42 RhoA/?-catenin complex. Notably, p-Tyr42 RhoA as well as ?-catenin was associated with the promoter of Vim, leading to increased expression of vimentin. In addition, stomach cancer patients harboring higher expressed p-Tyr42 Rho levels revealed the much poorer survival probability. Therefore, we propose that p-Tyr42 RhoA is crucial for transcriptional regulation of specific target genes in the nucleus by binding to their promoters and involved in tumorigenesis.

SUBMITTER: Kim JG 

PROVIDER: S-EPMC7788234 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

RhoA GTPase phosphorylated at tyrosine 42 by src kinase binds to β-catenin and contributes transcriptional regulation of vimentin upon Wnt3A.

Kim Jae-Gyu JG   Mahmud Shohel S   Min Jung Ki JK   Lee Yoon-Beom YB   Kim Hyunbin H   Kang Dong-Chul DC   Park Hwee-Seon HS   Seong Jihye J   Park Jae-Bong JB  

Redox biology 20201225


In the Wnt canonical pathway, Wnt3A has been known to stabilize β-catenin. In the non-canonical Wnt signaling pathway, Wnt is known to activate Rho GTPases. The correlation between canonical and non-canonical pathways by Wnt signaling, however, has not been well elucidated. Here, we identified that Wnt3A promoted superoxide generation, leading to Tyr42 phosphorylation of RhoA through activations of c-Src and Rho-dependent coiled coil kinase 2 (ROCK2) and phosphorylation of p47phox, a component o  ...[more]

Similar Datasets

| S-EPMC2735600 | biostudies-literature
| S-EPMC7087487 | biostudies-literature
| S-EPMC2684960 | biostudies-literature
| S-EPMC109286 | biostudies-literature
| S-EPMC2715999 | biostudies-literature
| S-EPMC8508824 | biostudies-literature
| S-EPMC5004446 | biostudies-literature
| S-EPMC6374103 | biostudies-literature
| S-EPMC3502191 | biostudies-literature
| S-EPMC3383259 | biostudies-literature