Inhibition of focal contact formation in cells transformed by p185neu

✍ Scribed by Su-Shun Lo; Su Hao Lo; Shao-Chun Wang; Mien-Chie Hung

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 111 KB
• Volume: 25
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199906)25:2<150::aid-mc10>3.0.co;2-q

✦ Synopsis

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 p130 CAS , 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 p185 neu . The cytoskeletal organization of the p185 neu -transformed cells was disrupted, and their morphology was dramatically altered. FAK, paxillin, and p130 CAS appeared to be tyrosine phosphorylated in both NIH/3T3 and B104-1-1. However, the phosphorylation levels of paxillin and p130 CAS 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.