| First Author | Yang H | Year | 2008 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 295 |
| Issue | 1 | Pages | G170-G178 |
| PubMed ID | 18467503 | Mgi Jnum | J:137546 |
| Mgi Id | MGI:3801219 | Doi | 10.1152/ajpgi.00492.2007 |
| Citation | Yang H, et al. (2008) Regulation of transforming growth factor beta-induced responses by protein kinase A in pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol 295(1):G170-G178 |
| abstractText | 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. |
