Molecular mechanism of induction of labor via placental protein kinase Nrk

2013 Fiscal Year Final Research Report

• Project/Area Number: 23657086
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: DENDA kimitoshi 東京工業大学, 生命理工学研究科, 助教 (50212064)
• Co-Investigator(Kenkyū-buntansha): KOMADA Masayuki 東京工業大学, 大学院・大学院・生命理工学研究科, 教授 (10225568)
• Project Period (FY): 2011 – 2012
• Keywords: Ser/Thrキナーゼ / ノックアウトマウス / 胎盤 / 分娩 / X染色体不活化

Research Abstract

Nrk(NIK-related kinase) is a functionally unknown Ser/Thr protein kinase. To elucidate the physiological roles of Nrk, we generated a strain of mice with targeted disruption of the Nrk gene in the X chromosome. The Nrk gene knockout causes overgrowth of the placenta, indicating that Nrk is a key regulator of placental cellular proliferation. In addition, when the Nrk-null fetuses were dominant, the pregnant dam failed to deliver offspring at term. Thus, Nrk appears to be important for performing parturition.
In order to investigate the molecular mechanisms leading to the Nrk knockout phenotype, protein expression levels in the Nrk knockout placenta were compared with those in wild type tissues by using high-performance two-dimensional electrophoresis methodology, and found several significant protein spots whose expression levels were enhanced or diminished significantly in the Nrk knockout placenta. Our examine whether placentas or fetus are essential for labor is now in progress.

Research Products

• [Journal Article] Nrk, an X-linked protein kinase in the germinal center kinase family, is required for placental development and fetoplacental induction of labor (2011)
  • Author(s): Denda K, Nakao-Wakabayashi K, Okamoto N, Kitamura N, Ryu JY, Tagawa Y, Ichisaka T, Yamanaka S, Komada M
  • Journal Title: J Biol Chem Volume: 19; 286(33) Pages: 28802-28810
  • DOI: 10.1074/jbc.M111.258160
  • Peer Reviewed
• [Presentation] 3P-0833 プロテインキナーゼNrk による乳腺上皮細胞の増殖抑制 (2013)
  • Author(s): 柳川享世, 稲谷卓也, 伝田公紀, 駒田雅之(東工大・生命理工)
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-05
• [Presentation] 2P-0452 分娩発来をもたらす胎盤特異的なプロテインキナーゼNrk が与るシグナル伝達機構の解明 (2013)
  • Author(s): 伝田公紀, 井田加奈子, 廣崎賢, 岡本直樹, 柳川享世, 林宜宏, 駒田雅之(東工大・院・生命理工)
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-03