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PTEN regulation by the Akt/GSK-3β axis during RANKL signaling

Title
PTEN regulation by the Akt/GSK-3β axis during RANKL signaling
Authors
Jang H.D.Noh J.Y.Shin J.H.Lin J.J.Lee S.Y.
Ewha Authors
이수영
SCOPUS Author ID
이수영scopus
Issue Date
2013
Journal Title
Bone
ISSN
8756-3282JCR Link
Citation
vol. 55, no. 1, pp. 126 - 131
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Phosphatase and tensin homolog (PTEN) negatively regulates phosphoinositide 3-kinase (PI3K)/Akt signaling as a lipid phosphatase for the second messenger phosphatidylinositol 3,4,5-triphosphate. We discovered recently that inactivating glycogen synthase kinase-3β (GSK-3β) via Akt plays an important role in receptor activator of nuclear factor κb ligand (RANKL)-induced osteoclastogenesis. However, the signaling link between GSK-3β and PTEN in RANKL signaling has not been revealed. Downregulating PTEN by RNA interference increases Akt and GSK-3β phosphorylation levels by RANKL, thereby promoting the formation of osteoclasts. PTEN phosphorylation at threonine 366 (T366) decreased gradually during RANKL-induced osteoclastogenesis, whereas PTEN protein levels were unaffected. Interestingly, the PTEN phosphorylation defective mutant (T366A) showed increased osteoclastogenesis, which is consistent with its lower phosphatase activity, compared to that of wild-type PTEN. Moreover, treatment with the GSK-3 inhibitor SB216763 suppressed PTEN phosphorylation levels and phosphatase activity and enhanced Akt phosphorylation. These data suggest that inhibiting GSK-3β during RANKL-induced osteoclastogenesis decreases PTEN phosphorylation, leading to enhanced osteoclast differentiation through Akt activation. © 2013 Elsevier Inc.
DOI
10.1016/j.bone.2013.02.005
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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