Roles played by a subset of integrin signaling molecules in cadherin-based cell-cell adhesion.
Integrins can intercommunicate with cadherins. Here, we examined their possible relationship by use of small interfering RNA-mediated protein knockdown in HeLa cells. We found that a subset of integrin signaling molecules, namely Fak and paxillin, but not p130 Crk-associated substrate or proline-rich tyrosine kinase 2, participate in processes regulating N-cadherin-based cell-cell adhesion. Paxillin was found to be required primarily for the recruitment of Fak to robust focal adhesions. Our results suggest that at least some signals involving Fak are linked to a mechanism down-regulating Rac1 activity at the cell periphery, which appears to be important for the formation of N-cadherin-based adhesions in motile cells. Our analyses simultaneously exemplified the essential role of Fak in the maintenance of cell-cell adhesions in collective cell migration, a type of migration occurring in embryonic development and carcinoma invasion.
Yano
Hajime
H
Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
Mazaki
Yuichi
Y
Kurokawa
Kazuo
K
Hanks
Steven K
SK
Matsuda
Michiyuki
M
Sabe
Hisataka
H
D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000502:physiology*; D051419:Paxillin; D010750:Phosphoproteins / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D050721:Proto-Oncogene Proteins c-cbl; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000502:physiology
D015820:Cadherins; D003598:Cytoskeletal Proteins; D016023:Integrins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C067419:CBL protein, human