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