The Regulatory Subunit PPP2R2A of PP2A Enhances Th1 and Th17 Differentiation through Activation of the GEF-H1/RhoA/ROCK Signaling Pathway.

ABSTRACT: Protein phosphatase 2A (PP2A) composed of a scaffold subunit, a catalytic subunit, and multiple regulatory subunits is a ubiquitously expressed serine/threonine phosphatase. We have previously shown that the PP2A catalytic subunit is increased in T cells from patients with systemic lupus erythematosus and promotes IL-17 production by enhancing the activity of Rho-associated kinase (ROCK) in T cells. However, the molecular mechanism whereby PP2A regulates ROCK activity is unknown. In this study, we show that the PP2A regulatory subunit PPP2R2A is increased in T cells from people with systemic lupus erythematosus and binds to, dephosphorylates, and activates the guanine nucleotide exchange factor GEF-H1 at Ser⁸⁸⁵, which in turn increases the levels of RhoA-GTP and the activity of

SUBMITTER: Pan W 

PROVIDER: S-EPMC8026731 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature