Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering (original) (raw)

Oncogene volume 17, pages 57–65 (1998)Cite this article

Abstract

Hepatocyte growth factor (HGF) markedly induced the spreading, dissociation and scattering of Madin–Darby canine kidney epithelial cells (MDCK) and human stomach adenocarcinoma cells (TMK1). Scattering of MDCK and TMK1 cells was induced by 12-**O**-tetradecanoyl-phorbol-13-acetate (PMA) and epidermal growth factor (EGF), respectively. In all these agent-stimulated cells, rapid activation of Raf-1, MAP kinase/ERK kinase (MEK), 41/43 kDa MAP kinases and p90rsk was commonly observed. In contrast, PMA neither induced the scattering nor activation of all these kinases in TMK1 cells. Pretreatment of MDCK and TMK1 cells with 2-(2-amino-3-methoxyphenyl) choromone (AMPC), a specific inhibitor of MEK, selectively inhibited the HGF-, PMA- and EGF-stimulated activities of MEK, 41/43 kDa MAP kinases and p90rsk in a dose dependent manner. AMPC-pretreatment, however, did not affect HGF-, PMA- or EGF-induced activation of Raf-1, nor HGF-induced activation of phosphatidylinositol 3-kinase in these cells. Importantly, HGF-, PMA- and EGF-induced scattering of MDCK and TMK1 cells was inhibited at doses of AMPC similar to those that gave comparable levels of inhibition of the activities of MEK, 41/43 kDa MAP kinases and p90rsk. These results suggest that activation of the 41/43 kDa MAP kinase signaling pathway is required for the motility response of MDCK and TMK1 cells induced by agents such as HGF, PMA and EGF.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 50 print issues and online access

$259.00 per year

only $5.18 per issue

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Author information

Author notes

  1. Susumu Tanimura
    Present address: Laboratory of Bioorganic Chemistry, The Institute of Physical and Chemical Research (RIKEN), Wako, 351-01, Saitama, Japan
  2. Yuji Chatani
    Present address: Minase Research Institute, Ono Pharmaceutical Co Ltd, Mishima-gun, Osaka, 618, Japan

Authors and Affiliations

  1. Laboratory of Cell Regulation, School of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki, 852-8131, Japan
    Susumu Tanimura, Rika Hoshino & Michiaki Kohno
  2. Gifu Pharmaceutical University, Mitahora-higashi, Gifu, 502, Japan
    Susumu Tanimura, Yuji Chatani, Masahiro Sato, Shin-ichi Watanabe, Tadashi Kataoka & Michiaki Kohno
  3. Biomedical Research Center, Osaka University Medical School, Suita, 565, Osaka, Japan
    Toshikazu Nakamura

Authors

  1. Susumu Tanimura
  2. Yuji Chatani
  3. Rika Hoshino
  4. Masahiro Sato
  5. Shin-ichi Watanabe
  6. Tadashi Kataoka
  7. Toshikazu Nakamura
  8. Michiaki Kohno

Rights and permissions

About this article

Cite this article

Tanimura, S., Chatani, Y., Hoshino, R. et al. Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering.Oncogene 17, 57–65 (1998). https://doi.org/10.1038/sj.onc.1201905

Download citation

Keywords

This article is cited by