TGF-β Signaling
Section leader
Aristidis Moustakas
Aris.Moustakas(AT)LICR.uu.se
Phone +46 18 160411
We investigate signaling pathways that regulate cell growth, differentiation and tumorigenesis in response to the extracellular protein, transforming growth factor beta (TGFβ). We study a) cellular mechanisms involved in regulation of Smad activity in the cytoplasm and the nucleus; b) novel mechanisms that mediate the tumor suppressor and pro-metastatic role of TGFβ. goes here.
TGFβ family members bind to their plasma membrane receptors which are serine/threonine kinases. TGFβ receptors then phosphorylate Smads and alternative signaling proteins in the cytoplasm. The TGFβ receptor-activated Smads (R-Smads) pair together with the Co-Smad (Smad4), and rapidly accumulate in the nucleus. The nuclear Smads then bind to chromatin and to many other transcription factors and regulate expression of a few hundred genes. When Smads finish their work in the nucleus, they exit to the cytoplasm and can be recycled for further signaling or can get degraded by proteasomes, thus ending their life cycle.
The core TGFβ-Smad pathway. The type I and type II receptors bind to TGFβ and activate Smad2/3, which then bind to Smad4 and accumulate in the nucleus. Together with other transcription factors (TF) the Smad complex regulates gene transcription (courtesy of R. Bergström).