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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.

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

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