Kim, Jae-Gyu Mahmud, Shohel Min, Jung Ki Lee, Yoon-Beom Kim, Hyunbin Kang, Dong-Chul Park, Hwee-Seon Seong, Jihye Park, Jae-Bong 2024-01-19T15:03:16Z 2024-01-19T15:03:16Z 2021-09-05 2021-04 2213-2317 https://pubs.kist.re.kr/handle/201004/117216 In the Wnt canonical pathway, Wnt3A has been known to stabilize beta-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 beta-catenin along with activations of RhoA and ROCK1. Concurrently, ROCK1 was able to phosphorylate GSK-3 beta 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 beta-catenin via the N-terminal domain of beta-catenin, thereby leading to the nuclear translocation of p-Tyr42 RhoA/beta-catenin complex. Notably, p-Tyr42 RhoA as well as beta-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. English ELSEVIER RhoA GTPase phosphorylated at tyrosine 42 by src kinase binds to beta-catenin and contributes transcriptional regulation of vimentin upon Wnt3A Article 10.1016/j.redox.2020.101842 1 REDOX BIOLOGY, v.40 REDOX BIOLOGY 40 scie scopus 000621105300001 2-s2.0-85098664089 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article p-Tyr42 RhoA &#946 -Catenin Wnt3A Superoxide GSK-3&#946 Src Cancer