Journal of Bioenergetics and Biomembranes

, Volume 32, Issue 3, pp 309–315 | Cite as

Regulation of Cellular Functions by Nucleoside Diphosphate Kinases in Mammals

  • Narimichi Kimura
  • Nobuko Shimada
  • Mitsugu Fukuda
  • Yasushi Ishijima
  • Hidetaka Miyazaki
  • Akio Ishii
  • Yohko Takagi
  • Naoshi Ishikawa
Article

Abstract

The role of nucleoside diphosphate (NDP) kinases in cell growth, differentiation, and tumormetastasis in relation to signal transduction was investigated. The essential role of NDP kinasein cell growth was validated by coupling between reduced NDP kinase levels, induced byantisense oligonucleotides, and the suppression of proliferative activity of a cultured cell line.In addition, because NDP kinase levels are often enhanced with development and differentiation,as has been demonstrated in postmitotic cells and tissues, such as the heart and brain, wefurther examined this possibility using the bone tissue (osteoblasts) and a cultured cell linePC12D. The enhanced NDP kinase accumulation was demonstrated in the matured osteoblastsin vivo and in vitro by immunohistochemistry. In PC12D cells neurite outgrowth took placein NDP kinase β-transfected clones without differentiation inducers, which was accompaniedby prolongation of doubling time. Neurite outgrowth, triggered by nerve growth factor and acyclic AMP analog, was down-regulated upon forced expression of inactive mutant NDPkinase by virtue of a dominant negative effect. NDP kinase α-transfected rat mammaryadenocarcinoma cells (MTLn3) and nm23-H2-transfected human oral squamous cell carcinomacells (LMF4) manifested reduced metastatic potential and were associated with an alteredsensitivity to environmental factors, such as motility and growth factors. NDP kinase α,compared to NDP kinase β, was involved in a wide variety of the cellular phenomena examined.Taken together, NDP kinase isoforms appear to elicit both their own respective and commoneffects. They may have an ability to lead cells to both proliferative and differentiated statesby modulating responsiveness to environmental factors, but their fate seems to depend on theirsurrounding milieu.

NDP kinase nm23 isoforms differentiation cell growth metastasis signal transduction 

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Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Narimichi Kimura
    • 1
  • Nobuko Shimada
    • 2
  • Mitsugu Fukuda
    • 2
  • Yasushi Ishijima
    • 2
  • Hidetaka Miyazaki
    • 2
  • Akio Ishii
    • 2
  • Yohko Takagi
    • 2
  • Naoshi Ishikawa
    • 2
  1. 1.Department of Gene Regulation and Protein FunctionTokyo Metropolitan Institute of GerontologyTokyoJapan
  2. 2.Department of Gene Regulation and Protein FunctionTokyo Metropolitan Institute of GerontologyTokyoJapan

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