Extracellular regulated signal kinase regulates cortactin ubiquitination and degradation in lung epithelial cells.

Cortactin, an actin-binding protein, is essential for cell growth and motility. We have shown that cortactin is regulated by reversible phosphorylation, but little is known regarding cortactin protein stability. Here, we show that lipopolysaccharide (LPS)-induced cortactin degradation is mediated by extracellular regulated signal kinase (Erk). LPS induces cortactin serine phosphorylation, ...
ubiquitination, and degradation in mouse lung epithelia, an effect abrogated by Erk inhibition. Cortactin is polyubiquitinated and degraded within the proteasome, whereas a cortactinK79R mutant exhibited proteolytic stability during cyclohexamide or LPS treatment. The E3 ligase subunit β-Trcp interacts with cortactin and its overexpression reduced cortactin protein levels, an effect attenuated by Erk inhibition. Over-expression of β-Trcp was sufficient to reduce the protective effects of exogenous cortactin on epithelial cell barrier integrity, an effect not observed after expression of a cortactinK79R mutant. These results provide evidence that LPS modulation of cortactin stability is coordinately regulated by stress kinases and the ubiquitin-proteasomal network.
Unknown
Date: Apr. 18, 2012
Download Curated Data For This Publication
131071
Switch View:
  • Interactions 2
  • PTM Genes 1