Fine tuning and cross-talking of TGF-beta signal by inhibitory Smads

J Biochem Mol Biol. 2005 Jan 31;38(1):9-16. doi: 10.5483/bmbrep.2005.38.1.009.


Transforming Growth Factor (TGF)-beta family, including TGF-beta, bone morphorgenic protein (BMP), and activn, plays an important role in essential cellular functions such as proliferation, differentiation, apoptosis, tissue remodeling, angiognesis, immune responses, and cell adhesions. TGF-beta predominantly transmits the signals through serine/threonine receptor kinases and cytoplasmic proteins called Smads. Since the discovery of TGF-beta in the early 1980s, the dysregulation of TGF-beta /Smad signaling has been implicated in the pathogenesis of human diseases. Among signal transducers in TGF-beta/Smad signaling, inhibitory Smads (I-Smads), Smad6 and Smad7, act as major negative regulators forming autoinhibitory feedback loops and mediate the cross-talking with other signaling pathways. Expressions of I-Smads are mainly regulated on the transcriptional levels and post-translational protein degradations and their intracellular levels are tightly controlled to maintain the homeostatic balances. However, abnormal levels of I-Smads in the pathological conditions elicit the altered TGF-beta signaling in cells, eventually causing TGF-beta-related human diseases. Thus, exploring the molecular mechanisms about the regulations of I-Smads may provide the therapeutic clues for human diseases induced by the abnormal TGF-beta signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Receptor Cross-Talk / physiology*
  • Receptors, Transforming Growth Factor beta / physiology
  • Signal Transduction*
  • Transforming Growth Factor beta / physiology*


  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta