Dynamics of TGF-p signaling reveal adaptive and pulsatile behaviors reflected in the nuclear localization of transcription factor Smad4

摘要

During embryonic development, signaling pathways allow communication between cells to establish positional information within the embryo. The timing and duration of signaling play an important role in the establishment of cell fates (1, 2); however, the acquisition of knowledge of these dynamics has lagged behind dissection of pathway components and their biochemical interactions. The TGF-p signaling pathway plays a vital role in development and is essential for early events, such as mesoderm induction and dorsal-ventral patterning. This pathway also has long been implicated in cancer, with several pathway components having been identified as tumor suppressors. More detailed knowledge of pathway dynamics will shed light on issues of both fundamental and therapeutic importance. Here, we show that the dynamics of TGF-p signaling are adaptive or pulsatile depending on the context and that these dynamics are reflected in the nuclear localization of the transcriptional cofactor Smad4 but not the Smads that are activated by the receptors (R-Smads).