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.
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#)
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