PP2A-Mediated GSK3β Dephosphorylation Is Required for Protocadherin-7-Dependent Regulation of Small GTPase RhoA in Osteoclasts.

ABSTRACT: Protocadherin-7 (Pcdh7) is a member of the non-clustered protocadherin δ1 subgroup of the cadherin superfamily. Pcdh7 has been revealed to control osteoclast differentiation by regulating Rho-family small GTPases, RhoA and Rac1, through its intracellular SET binding domain. However, the mechanisms by which small GTPases are regulated downstream of Pcdh7 remain unclear. Here, we demonstrate that protein phosphatase 2A (PP2A)-mediated dephosphorylation of Glycogen synthase kinase-3β (GSK3β) is required for Pcdh7-dependent activation of RhoA during osteoclast differentiation. Pcdh7-deficient (Pcdh7^-/-) cells showed impaired PP2A activity, despite their normal expression of PP2A. GSK3β, whose activity is regulated by its inhibitory phosphorylation at Ser9, was dephosphorylated durin

SUBMITTER: Kim H 

PROVIDER: S-EPMC10417323 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature