Regulation of transforming growth factor β-induced responses by protein kinase A in pancreatic acinar cells

Huibin Yang, Cheong J. Lee, Lizhi Zhang, Maria Dolors Sans, Diane M. Simeone

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

TGF-β is an important regulator of growth and differentiation in the pancreas and has been implicated in pancreatic tumorigenesis. We have recently demonstrated that TGF-β can activate protein kinase A (PKA) in mink lung epithelial cells (Zhang L, Duan C, Binkley C, Li G, Uhler M, Logsdon C, Simeone D. Mol Cell Biol 24: 2169-2180, 2004). In this study, we sought to determine whether TGF-β activates PKA in pancreatic acinar cells, the mechanism by which PKA is activated, and PKA's role in TGF-β-mediated growth regulatory responses. TGF-β rapidly activated PKA in pancreatic acini while having no effect on intracellular cAMP levels. Coimmunoprecipitation experiments demonstrated a physical interaction between a Smad3/Smad4 complex and the regulatory subunits of PKA. TGF-β also induced activation of the PKA-dependent transcription factor CREB. Both the specific PKA inhibitor H89 and PKI peptide significantly blocked TGF-β's ability to activate PKA and CREB. TGF-β-mediated growth inhibition and TGF-β-induced p21 and SnoN expression in pancreatic acinar cells were blocked by H89 and PKI peptide. This study demonstrates that this novel cross talk between TGF-β and PKA signaling pathways may play an important role in regulating TGF-β signaling in the pancreas.

Original languageEnglish (US)
Pages (from-to)G170-G178
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume295
Issue number1
DOIs
StatePublished - Jul 2008

Keywords

  • Sample keywords

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'Regulation of transforming growth factor β-induced responses by protein kinase A in pancreatic acinar cells'. Together they form a unique fingerprint.

Cite this