Inhibitory machinery for the TGF-ß family signaling pathway.

ABSTRACT

Transforming growth factor-ß (TGF-ß) family signaling regulates cell growth and differentiation of many different cell types and is widely involved in the regulation of homeostasis during both embryogenesis and adult life. Therefore, aberrant TGF-ß family signal transduction is linked to congenital disorders, tumorigenicity, and fibrosis, which can be life-threatening. A specific receptor-ligand complex initiates transduction of TGF-ß family signaling to the nucleus via intracellular signal molecules, mainly Smads, whereby a number of bioactivities such as wound healing, immunomodulation, apoptosis, and angiogenesis are controlled. To avoid an excess of TGF-ß family signaling in cells, the duration and intensity of the TGF-ß family signal appear to be subject to elaborate regulation. In this paper, we describe recent advances in the understanding of how TGF-ß family signals are perturbed and terminated to maintain homeostasis in cells.