TGF-beta signaling pathway
Tuesday 7 October 2003
Transforming growth factor-beta proteins (TGF-beta proteins or TGFBs) are key players in a large variety of physiological and disease processes.
MADHs (SMIF, SMADs)
The gene encoding the type II TGF-β receptor is inactivated in 70% or more of colon cancers that develop in patients with HNPCC, in sporadic colon cancers with microsatellite instability (discussed in conjunction with DNA repair genes), and in gastric cancers that develop in HNPCC patients.
SMAD4, which encodes a component of the TGF-β growth-inhibitory signal transduction pathway, is inactivated in approximately 50% of pancreatic cancers, while mutations in SMAD2, another component of the pathway, are present in some colorectal tumors. Because of its association with pancreatic cancers, SMAD4 was originally designated DPC4, deleted in pancreatic cancer.
Loss-of-function mutations in Growth Differentiation Factor-1 (GDF1) are associated with congenital heart defects (17924340)
Luo K. Ski and SnoN: negative regulators of TGF-beta signaling. Curr Opin Genet Dev. 2004 Feb;14(1):65-70. PMID: 15108807
Attisano L, Wrana JL. Signal transduction by the TGF-beta superfamily. Science. 2002 May 31;296(5573):1646-7. PMID: 12040180
Akhurst RJ, Derynck R. TGF-beta signaling in cancer—a double-edged sword. Trends Cell Biol. 2001 Nov;11(11):S44-51. PMID: 11684442
Souchelnytskyi S, Moustakas A, Heldin CH. TGF-beta signaling from a three-dimensional perspective: insight into selection of partners. Trends Cell Biol. 2002 Jul;12(7):304-7. PMID: 12185845