TGF-P Signaling Pathway

Varady G, Sarkadi B, Fatyol K. TTRAP is a novel component of the non-canonical TRAF6-TAK1 TGF-p signaling pathway. PLoS One. 2011 6(9) e25548. doi 10.1371/ joumal.pone.0025548. 

SB-505124, both of which target the TbRI kinase domain, are in preclinical use. An alternative approach to inhibiting TGF- 3 signaling is to focus on the tumor suppressive function of this pathway. Promising future treatments will focus on pathways that are activated when the TGF-P signaling tumor suppressor pathway is inactivated. Examples are inhibitors to wnt signaling, CDK4 activation and IL-6. 

TGF-Pl, is the most abundant member of the TGF-P superfamily (Janssens et al, 2005). It impacts cell proliferation, differentiation, and apoptosis of both chondrocytes and osteoblasts (Selvamurugan et al, 2004). TGF-Pl signaling pathway occurs through Smad activation as well as through non-Smad pathways including activation of the ERK, JNK, and p38 MAPK pathways (Moustakas and Heldin, 2005, Blaney Davidson et al, 2007). TGF-P is found in the ECM surrounding osteoblasts as well as in chondrocytes. 

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