The Catalytic Activity of the Src Family Kinases Is Required to Disrupt Cadherin-dependent Cell–Cell Contacts
AUTOR(ES)
Owens, Dewi W.
FONTE
The American Society for Cell Biology
RESUMO
Despite the importance of epithelial cell contacts in determining cell behavior, we still lack a detailed understanding of the assembly and disassembly of intercellular contacts. Here we examined the role of the catalytic activity of the Src family kinases at epithelial cell contacts in vitro. Like E- and P-cadherin, Ca2+ treatment of normal and tumor-derived human keratinocytes resulted in c-Yes (and c-Src and Fyn), as well as their putative substrate p120CTN, being recruited to cell–cell contacts. A tyrosine kinase inhibitor with selectivity against the Src family kinases, PD162531, and a dominant-inhibitory c-Src protein that interferes with the catalytic function of the endogenous Src kinases induced cell–cell contact and E-cadherin redistribution, even in low Ca2+, which does not normally support stable cell–cell adhesion. Time-lapse microscopy demonstrated that Src kinase inhibition induced stabilization of transiently formed intercellular contacts in low Ca2+. Furthermore, a combination of E- and P-cadherin-specific antibodies suppressed cell–cell contact, indicating cadherin involvement. As a consequence of contact stabilization, normal cells were unable to dissociate from an epithelial sheet formed at high density and repair a wound in vitro, although individual cells were still motile. Thus, cadherin-dependent contacts can be stabilized both by high Ca2+ and by inhibiting Src activity in low (0.03 mM) Ca2+ in vitro.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=14756Documentos Relacionados
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