Matrix/Integrin Interaction Activates the Mitogen-activated Protein Kinase, p44
and p42
(*)
- Noritsugu Morino(1),
- Toshihide Mimura(1),
- Ken Hamasaki(1),
- Kazuyuki Tobe(1),
- Kohjiro Ueki(1),
- Kanako Kikuchi(2),
- Kazuhiko Takehara(2),
- Takashi Kadowaki(1),
- Yoshio Yazaki(1) and
- Yoshihisa Nojima(1)(§)
- From the (1)Third Department of Internal Medicine and the
- (2)Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo 113, Japan
- § To whom correspondence should be addressed: The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Tel.: 03-3815-5411; Fax: 03-5684-3987.
Abstract
Cell adhesion to extracellular matrix proteins is a dynamic process leading to dramatic changes in the cell phenotype. Integrins
are one of the major receptor families that mediate cell-matrix contact. Evidence that integrins can act as signal transducing
molecules has accumulated over the past few years. We report here that p44
and p42
mitogen-activated protein (MAP) kinases are rapidly phosphorylated on tyrosine residues upon adhesion of human skin fibroblasts
to fibronectin or upon cross-linking of β1 integrins with antibody. The tyrosine phosphorylation of both kinases is associated
with increased enzymatic activity. Pretreatment of the cells with cytochalasin D, which selectively disrupts the network of
the actin filaments, completely inhibits this adhesion-mediated MAP kinase activation. Thus, our findings indicate that ligation
of β1 integrins induces an increase in both tyrosine phosphorylation and enzymatic activity of p44
and p42
MAP kinases, and that the integrity of the actin cytoskeleton is essential in this process. Since MAP kinase behaves as a
convergence point for diverse receptor-initiated signaling events at the plasma membrane, this serine/threonine kinase plays
a key role and helps to account for the diversity of integrin-dependent cell functions.
Footnotes
-
↵* This work was supported by Grants-in-aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan, and by Japan Rheumatism Foundation Grant for 1993 (to Y. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- ECM
-
extracellular matrix protein
- MAP
-
mitogen-activated protein
- HSF
-
human skin fibroblast
- FN
-
fibronectin
- MBP
-
myelin basic protein
- PLL
-
poly-L-lysine
- ERK
-
extracellular signal-regulated kinase
- DMEM
-
Dulbecco's modified Eagle's medium
- PBS
-
phosphate-buffered saline
- PAGE
-
polyacrylamide gel electrophoresis
- MHC
-
major histocompatibility complex.
-
- Received August 8, 1994.
- Revision received October 6, 1994.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
