TGFbeta-mediated signaling and transcriptional regulation in pancreatic development and cancer.
Transforming growth factor-beta (TGFbeta) plays a critical role in pancreatic development and cell proliferation. Binding of TGFbeta to its membrane receptor kinases activates the Smad signaling proteins, allowing them to translocate to the nucleus and participate in the transcriptional control of TGFbeta target genes. In addition, there is an increasing number of cellular mechanisms affecting the final response of a cell to TGFbeta. This includes crosstalk with other signaling pathways and the induction of TGFbeta early response genes, such as the TGFbeta-inducible early response gene (TIEG) family of transcription factors. Like the Smads, TIEGs behave as downstream effector proteins in TGFbeta-mediated pancreatic growth control. The discovery of the Smads and TIEGs has provided new insights into TGFbeta-regulated functions. Their significance in pancreatic development and cancer is discussed in this review.
Ellenrieder
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Mayo Clinic, Rochester, Minnesota, USA.
Fernandez Zapico
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ME
Urrutia
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