期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 281, 期 1, 页码 C311-C319出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.2001.281.1.C311
关键词
transforming growth factor-beta
资金
- NIDDK NIH HHS [5P30-DK-34933, K08-DK-02637-01] Funding Source: Medline
Transforming growth factor-beta (TGF-beta) inhibits pancreatic acinar cell growth. In many cell types, TGF-beta mediates its growth inhibitory effects by activation of Smad proteins. Recently, it has been reported that Smad proteins may interact with the mitogen-activated protein (MAP) kinase signaling pathways. In this study, we report on the interactions between the TGF-beta and MAP kinase signaling pathways in isolated rat pancreatic acinar cells. TGF-beta activated the MAP kinases extracellular signal-related kinases (ERKs) and p38 in pancreatic acinar cells, but had no effect on c-jun NH2-terminal kinase activity. Activation of MAP kinase by TGF-beta was maximal 4 h after treatment. The ability of TGF-beta to activate ERKs was concentration dependent and dependent on protein synthesis. TGF-beta 's stimulation of ERK activation was blocked by PD-98059, an inhibitor of MAP kinase kinase 1, and by adenoviral transfer of dominant negative Ras(N17). Furthermore, adenoviral-mediated expression of dominant negative Smad4 blocked the ability of TGF-beta to activate acinar cell MAP kinase, demonstrating that this activation is downstream of Smads. The biological relevance of ERK activation by TGF-beta was indicated by demonstrating that inhibition of ERK signaling by PD-98059 blocked the ability of TGF-beta to activate the transcription factor activator protein-1. These studies provide new insight into the signaling mechanisms by which TGF-beta mediates biological actions in pancreatic acinar cells.
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