論文

査読有り
2010年6月

LKB1 Suppresses p21-activated Kinase-1 (PAK1) by Phosphorylation of Thr(109) in the p21-binding Domain

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Atsuko Deguchi
  • ,
  • Hiroyuki Miyoshi
  • ,
  • Yasushi Kojima
  • ,
  • Katsuya Okawa
  • ,
  • Masahiro Aoki
  • ,
  • Makoto M. Taketo

285
24
開始ページ
18283
終了ページ
18290
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M109.079137
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

The serine/threonine protein kinase LKB1 is a tumor suppressor gene mutated in Peutz-Jeghers syndrome patients. The mutations are found also in several types of sporadic cancer. Although LKB1 is implicated in suppression of cell growth and metastasis, the detailed mechanisms have not yet been elucidated. In this study, we investigated the effect of LKB1 on cell motility, whose acquisition occurs in early metastasis. The knockdown of LKB1 enhanced cell migration and PAK1 activity in human colon cancer HCT116 cells, whereas forced expression of LKB1 in Lkb1-null mouse embryonic fibroblasts suppressed PAK1 activity and PAK1-mediated cell migration simultaneously. Notably, LKB1 directly phosphorylated PAK1 at Thr(109) inthep21-binding domain in vitro. The phosphomimetic T109E mutant showed significantly lower protein kinase activity than wild-type PAK1, suggesting that the phosphorylation at Thr(109) by LKB1 was responsible for suppression of PAK1. Consistently, the nonphosphorylatable T109A mutant was resistant to suppression by LKB1. Furthermore, we found that PAK1 was activated in the hepatocellular carcinomas and the precancerous liver lesions of Lkb1(+/-) mice. Taken together, these results suggest that PAK1 is a direct down-stream target of LKB1 and plays an essential role in LKB1-induced suppression of cell migration.

Web of Science ® 被引用回数 : 25

リンク情報
DOI
https://doi.org/10.1074/jbc.M109.079137
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20400510
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000278453900021&DestApp=WOS_CPL

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