TGFβ intercepts nuclear glycogen synthase kinase 3β to inhibit PDGF-induced DNA synthesis in mesangial cells

Falguni Das, Lenin Mahimainathan, Nandini Ghosh-Choudhury, Balachandar Venkatesan, Balakuntalam S. Kasinath, Hanna E. Abboud, Goutam Ghosh Choudhury

Producción científica: Articlerevisión exhaustiva

7 Citas (Scopus)

Resumen

Here, we demonstrate a mechanism of TGFβ-mediated inhibition of PDGF-induced DNA synthesis in mesangial cells. TGFβ significantly inhibited nuclear Akt phosphorylation without any effect on PDGF-stimulated phosphorylation of PDGFR at PI 3 kinase binding site (Tyr-751). Remarkably, TGFβ inhibited cyclin D1 and cyclin E expression with concomitant decrease in CDK2 activity induced by PDGF. More importantly, we demonstrate that TGFβ significantly abolished Akt-mediated serine-9 phosphorylation of glycogen synthase kinase 3β (GSK3β), thus prevented its inactivation. Expression of inactive GSK3βK85R mutant increased cyclin D1 expression and DNA synthesis similar to PDGF. These results provide the first evidence that TGFβ intercepts Akt kinase activity in the nucleus to block inactivation of GSK3β, leading to attenuation of PDGF-induced CDK2 activity and DNA synthesis.

Idioma originalEnglish (US)
Páginas (desde-hasta)5259-5267
Número de páginas9
PublicaciónFEBS Letters
Volumen581
N.º27
DOI
EstadoPublished - nov 13 2007

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Cell Biology

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