Tyrosine phosphorylation-dependent PI 3 kinase/Akt signal transduction regulates TGFβ-induced fibronectin expression in mesangial cells

Goutam Ghosh Choudhury, Hanna E. Abboud

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

TGFβ stimulates expression of fibronectin in various cells, including mesangial cells. The mechanism by which TGFβ exerts this effect is not fully understood. We investigated the involvement of tyrosine phosphorylation and the phosphatidylinositol (PI) 3 kinase/Akt signalling pathway in this process. TGFβ increased tyrosine phosphorylation, resulting in activation of PI 3 kinase in mesangial cells. Inhibition of tyrosine phosphorylation blocked TGFβ-induced fibronectin expression. Inhibition of PI 3 kinase activity also prevented fibronectin expression induced by TGFβ. Furthermore, expression of constitutively active PI 3 kinase by adenovirus-mediated gene transfer increased fibronectin expression similar to TGFβ. TGFβ stimulated Akt serine threonine kinase in a tyrosine kinase- and PI 3 kinase-dependent manner. Inhibition of TGFβ-induced Akt activity by adenovirus-mediated expression of a dominant-negative mutant of Akt abolished expression of fibronectin. Dominant-negative PI 3 kinase or dominant-negative Akt inhibited TGFβ-induced fibronectin transcription. In contrast, and similarly to TGFβ, expression of constitutively active PI 3 kinase or constitutively active Akt increased transcription of fibronectin, confirming a prominent role of these kinases in expression of fibronectin. These data provide the evidence that activation of TGFβ receptor serine threonine kinase stimulates the PI 3 kinase/Akt pathway in a tyrosine phosphorylation-dependent manner and define a role for the same signal transduction pathway in TGFβ-induced fibronectin expression.

Original languageEnglish (US)
Pages (from-to)31-41
Number of pages11
JournalCellular Signalling
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2004

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Keywords

  • Akt
  • Fibronectin
  • Mesangial cell
  • TGFβ
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Cell Biology

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