title: Cdc42 and Rac small G proteins activated by trans-interactions of nectins are involved in activation of c-Jun N-terminal kinase, but not in association of nectins and cadherin to form adherens junctions, in fibroblasts.
abstract: BACKGROUND
  Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules which associate with cadherins to form adherens junctions (AJs) in epithelial cells and fibroblasts. Nectin-1 and -3 are members of the nectin family which most strongly trans-interact, causing cell-cell adhesion. The trans-interaction between nectin-1 and -3 induces the activation of both Cdc42 and Rac small G proteins in epithelial cells. We studied the roles of Cdc42 and Rac activated in this way in L fibroblasts stably expressing both nectin-1 and E-cadherin (nectin-1-EL cells).
  
  
  RESULTS
  The trans-interaction between nectin-1 and -3 induced the activation of Cdc42 and Rac in nectin-1-EL cells. Cdc42, and presumably Rac, activated in this way, induced the activation of c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein (MAP) kinase or extracellular signal-regulated kinase (ERK). Cdc42 or Rac was not essential for the association of nectin-1 and E-cadherin to form AJs. Reorganization of the actin cytoskeleton was not required for the association of nectin-1 and E-cadherin.
  
  
  CONCLUSIONS
  These results indicate that Cdc42 and Rac activated by the trans-interaction of nectins selectively induce the activation of JNK, but are not essential for the association of nectins and cadherin to form AJs in fibroblasts.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honda
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kawakatsu
authors.forename: Atsunori
authors.initials: A
authors.lastname: Fukuhara
authors.forename: Kenji
authors.initials: K
authors.lastname: Irie
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Matsuda
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007091:Image Processing, Computer-Assisted; D048031:JNK Mitogen-Activated Protein Kinases; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000075983:Nectins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011554:Pseudopodia; D014162:Transfection; D000077191:Wortmannin; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000730:Androstadienes; D015820:Cadherins; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D049452:Green Fluorescent Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D000077191:Wortmannin