Glycogen synthase kinase 3β interacts with and phosphorylates the spindle-associated protein astrin

Tai Shan Cheng, Yun Ling Hsiao, Ching Chih Lin, Chang Tze Ricky Yu, Ching Mei Hsu, Mau Sun Chang, Chu I. Lee, Chi Ying F. Huang, Shen Long Howng, Yi Ren Hong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Emerging evidence shows that glycogen synthase kinase 3β (GSK3β) is involved in mitotic division and that inhibiting of GSK3β kinase activity causes defects in spindle microtubule length and chromosome alignment. However, the purpose of GSK3β involvement in spindle microtubule assembly and accurate chromosome segregation remains obscure. Here, we report that GSK3β interacts with the spindle-associated protein Astrin both in vitro and in vivo. Additionally, Astrin acts as a substrate for GSK3β and is phosphorylated at Thr-111, Thr-937 ((S/T)P motif) and Ser-974/Thr-978 ((S/T)XXX(S/T)-p motif; p is a phosphorylatable residue). Inhibition of GSK3β impairs spindle and kinetochore accumulation of Astrin and spindle formation at mitosis, suggesting that Astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by GSK3β. Conversely, depletion of Astrin by small interfering RNA has no detectable influence on the localization of GSK3β. Interestingly, in vitro assays demonstrated that Astrin enhances GSK3β-mediated phosphorylation of other substrates. Moreover, we showed that coexpression of Astrin and GSK3β differentially increases GSK3β-mediated Tau phosphorylation on an unprimed site. Collectively, these data indicate that GSK3β interacts with and phosphorylates the spindle-associated protein Astrin, resulting in targeting Astrin to the spindle microtubules and kinetochores. In turn, the GSK3β-Astrin complex may also facilitate further physiological and pathological phosphorylation.

Original languageEnglish
Pages (from-to)2454-2464
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number4
DOIs
StatePublished - 25 Jan 2008

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