ROCK2 regulates bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway

Abstract

Increased neurogenesis by promoting proliferation of neural precursor cells in the adult dentate gyrus might be beneficial for the treatment of psychiatric disorders. Results demonstrate that bFGF is necessary for the proliferation of neural precursor cells and that the glycogen synthase kinase-3β (GSK-3β) and β-catenin pathway plays a role in it. However, the detailed mechanism of proliferation of neural precursor cells remains unclear. To elucidate that mechanism, we investigated the role of Rho-associated coiled-coil kinase (ROCK) in bFGF-induced proliferation using SH-SY5Y cells as a model of neural precursor-like cells. Y27632, a specific inhibitor of ROCK, decreased bFGF-induced proliferation. Lithium (Li), an inhibitor of GSK-3β, recovered Y27632-decreased proliferation and quercetin (Que), an inhibitor of β-catenin pathway, reversed the recovery effect of Li. Both nuclear β-catenin and cyclin D1 expression were altered by bFGF, Y27632, Li, and Que in parallel with the case of proliferation. Furthermore, bFGF inactivated GSK-3β through increasing the phosphorylation of Ser 9 on GSK-3β, which is reversed by Y27632 through increased phosphorylation of Tyr 216 on GSK-3β. ROCK has two subtypes: ROCK1 and ROCK2. Investigation with siRNA for ROCKs showed that ROCK2 is involved in bFGF-induced proliferation, but not ROCK1. These results suggest that ROCK2 might mediate bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway. Further investigation of detailed mechanisms regulating the ROCK2/GSK-3β/β-catenin pathway might engender the development of new therapeutic targets of psychiatric disorders.

Basic fibroblast growth factor is pro‐adipogenic in rat skeletal muscle progenitor clone, 2G11 cells

“…; Boku et al . ), it is possible that the pro‐adipogenic effect of bFGF on 2G11 cells would be mediated through activation of MAPK and GSK3β, and subsequent phosphorylation of C/EBPβ and C/EBPδ, resulting in an up‐regulation of both C/EBPα and PPARγ as observed in the present study.…”

ROCK2 promotes HCC proliferation by CEBPD inhibition through phospho‐GSK3β/β‐catenin signaling

“…4 A). In addition, it has been reported that Rock2 can regulate its substrate protein by affecting the phosphorylation of Gsk‐3β [16]. Therefore, we speculated that Rock2 regulated CEBPD‐mediated HCC proliferation via the pGSK‐3β pathway.…”

Rho Kinases in Cardiovascular Physiology and Pathophysiology

“…In addition, both ROCK1 and ROCK2 mediate insulin-stimulated insulin receptor substrate (IRS)-1 phosphorylation, but only ROCK2 binds directly to IRS-1. 62 Moreover, functional differences between ROCK1 and ROCK2 have been reported in fibroblasts, 63–66 smooth muscle cells, 61,67 endothelial cells, 68–72 keratinocytes, 73–75 adipocytes, 62,65 neurons 66 and cancer cells. 76,77 These studies reveal that ROCK1 and ROCK2 have functional differences in regulating actin cytoskeleton, but the underlying mechanisms are not fully understood, which could be explained by the facts that both isoforms are expressed at different levels, distributed at different subcellular locations, and/or they have different interaction partners in individual cell types.…”