Faculty Collaboration Database

Regulation of transforming growth factor beta-induced responses by protein kinase A in pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol 2008 Jul;295(1):G170-G178

Date

05/10/2008

Pubmed ID

18467503

Pubmed Central ID

PMC2494718

DOI

10.1152/ajpgi.00492.2007

Scopus ID

2-s2.0-51149095049 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

TGF-beta is an important regulator of growth and differentiation in the pancreas and has been implicated in pancreatic tumorigenesis. We have recently demonstrated that TGF-beta 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-beta activates PKA in pancreatic acinar cells, the mechanism by which PKA is activated, and PKA's role in TGF-beta-mediated growth regulatory responses. TGF-beta 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-beta also induced activation of the PKA-dependent transcription factor CREB. Both the specific PKA inhibitor H89 and PKI peptide significantly blocked TGF-beta's ability to activate PKA and CREB. TGF-beta-mediated growth inhibition and TGF-beta-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-beta and PKA signaling pathways may play an important role in regulating TGF-beta signaling in the pancreas.

Author List

Yang H, Lee CJ, Zhang L, Sans MD, Simeone DM

MESH terms used to index this publication - Major topics in bold

Animals
Cells, Cultured
Cyclic AMP
Cyclic AMP Response Element-Binding Protein
Cyclic AMP-Dependent Protein Kinases
Gene Expression Regulation
Male
Mice
Mice, Inbred C57BL
Pancreas, Exocrine
Proto-Oncogene Proteins
Signal Transduction
Transforming Growth Factor beta
rho GTP-Binding Proteins