Phosphorylation of the tubulin-binding protein, stathmin, by Cdk5 and MAP kinases in the brain

Kanehiro Hayashi, Yong Pan, Hongjun Shu, Toshio Ohshima, Janice W. Kansy, Charles L. White, Carol A. Tamminga, André Sobel, Patrick A. Curmi, Katsuhiko Mikoshiba, James A. Bibb*

*この研究の対応する著者

研究成果: Article査読

44 被引用数 (Scopus)

抄録

Regulation of cytoskeletal dynamics is essential to neuronal plasticity during development and adulthood. Dysregulation of these mechanisms may contribute to neuropsychiatric and neurodegenerative diseases. The neuronal protein kinase, cyclin-dependent kinase 5 (Cdk5), is involved in multiple aspects of neuronal function, including regulation of cytoskeleton. A neuroproteomic search identified the tubulin-binding protein, stathmin, as a novel Cdk5 substrate. Stathmin was phosphorylated by Cdk5 in vitro at Ser25 and Ser38, previously identified as mitogen-activated protein kinase (MAPK) and p38 MAPKδ sites. Cdk5 predominantly phosphorylated Ser38, while MAPK and p38 MAPKδ predominantly phosphorylated Ser25. Stathmin was phosphorylated at both sites in mouse brain, with higher levels in cortex and striatum. Cdk5 knockout mice exhibited decreased phospho-Ser38 levels. During development, phospho-Ser25 and -Ser38 levels peaked at post-natal day 7, followed by reduction in total stathmin. Inhibition of protein phosphatases in striatal slices caused an increase in phospho-Ser25 and a decrease in total stathmin. Interestingly, the prefrontal cortex of schizophrenic patients had increased phospho-Ser25 levels. In contrast, total and phospho-Ser25 stoichiometries were decreased in the hippocampus of Alzheimer's patients. Thus, microtubule regulatory mechanisms involving the phosphorylation of stathmin may contribute to developmental synaptic pruning and structural plasticity, and may be involved in neuropsychiatric and neurodegenerative disorders.

本文言語English
ページ(範囲)237-250
ページ数14
ジャーナルJournal of neurochemistry
99
1
DOI
出版ステータスPublished - 2006 10
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 細胞および分子神経科学

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