期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 295, 期 1, 页码 G170-G178出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00492.2007
关键词
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资金
- NIDDK NIH HHS [R01 DK-061507] Funding Source: Medline
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.
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