Somatic Acquisition and Signaling of TGFBR1*6A in Cancer

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Abstract
Transforming growth factor β (TGF-β) is a potent naturally occurring inhibitor of cell growth. It exerts its action by binding to type I (TGFBR1) and type II (TGFBR2) transmembrane receptors located on the cell membrane. Intracellular signaling begins once TGF-β has bound to the TGFBR1/TGFBR2 complex. TGFBR2 activates TGFBR1, which acts as the initiator of intracellular responses. Mothers against decapentaplegic homolog 2 (SMAD2) and SMAD3 are subsequently activated by TGFBR1 and form complexes with SMAD4. Activated SMAD complexes enter the nucleus where they regulate the activity of target genes.1 There is evidence that TGF-β related proteins activate not only SMADs but also other signaling pathways.2