Transforming growth factor-beta proteins (TGF-beta proteins or TGFBs) are key players in a large variety of physiological and disease processes.
It signals through transmembrane receptor serine/threonine kinases to activate novel signaling intermediates called Smad or MADHs proteins, which then modulate transcription of target genes.
Members
MADHs (SMIF, SMADs)
Pathology
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)
Reviews
ten Dijke P, Arthur HM. Extracellular control of TGFbeta signalling in vascular development and disease. Nat Rev Mol Cell Biol. 2007 Nov;8(11):857-69. PMID: 17895899
Arteaga CL. Inhibition of TGFbeta signaling in cancer therapy. Curr Opin Genet Dev. 2006 Feb;16(1):30-7. PMID: 16377175
Luo K. Ski and SnoN: negative regulators of TGF-beta signaling. Curr Opin Genet Dev. 2004 Feb;14(1):65-70. PMID: 15108807
Byfield SD, Roberts AB. Lateral signaling enhances TGF-beta response complexity. Trends Cell Biol. 2004 Mar;14(3):107-11. PMID: 15055198
Serra R, Chang C. TGF-beta signaling in human skeletal and patterning disorders. Birth Defects Res Part C Embryo Today. 2003 Nov;69(4):333-51. PMID: 14745974
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
Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 2000 Dec;1(3):169-78. PMID: 11252892
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