title: Inhibition of focal contact formation in cells transformed by p185neu.
abstract: Signaling pathways mediated by adhesive molecules are tightly associated with cytoskeletal organization and cell growth regulation. Focal adhesion kinase (FAK) plays a prominent role in the adhesion signaling pathway through its tyrosine kinase activity and protein-protein interaction with other signaling molecules, including src, paxillin, and p130CAS, and other proteins. We explored the roles of these signaling molecules in the transformation of B104-1-1 cells, an NIH/3T3-derived cell line transformed by activated rat p185neu. The cytoskeletal organization of the p185neu-transformed cells was disrupted, and their morphology was dramatically altered. FAK, paxillin, and p130CAS appeared to be tyrosine phosphorylated in both NIH/3T3 and B104-1-1. However, the phosphorylation levels of paxillin and p130CAS were lower in B104-1-1 cells than in NIH/3T3 cells. Surprisingly, the association between FAK and paxillin was enhanced in B104-1-1 cells, suggesting reorganization of protein-protein interaction modulated by protein phosphorylation. Our results showed that even though cellular transformation by src and neu has similar consequences, such as focal adhesion disassembly and increased metastasis potential, the molecular events underlying the signaling pathways can be dramatically different.
authors.affiliation: Division of General Surgery Veterans General Hospital-Taipei and National Yang Ming University, Taiwan.
authors.forename: S S
authors.initials: SS
authors.lastname: Lo
authors.forename: S H
authors.initials: SH
authors.lastname: Lo
authors.forename: S C
authors.initials: SC
authors.lastname: Wang
authors.forename: M C
authors.initials: MC
authors.lastname: Hung
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018734:Genes, erbB-2; D016023:Integrins / Q000378:metabolism; D051379:Mice; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: C493842:Bcar1 protein, mouse; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins; D016023:Integrins; D051419:Paxillin; D010750:Phosphoproteins; D011506:Proteins; C496062:Pxn protein, mouse; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse