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TGF β – an excellent servant but a bad master

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Figure

Figure 1 TGF-β synthesis and activation. TGF-βs are synthesized as inactive precursors that contain pre-region (Signal peptide) and pro-region(N terminal peptide - LAP)
Figure 2 TGF-β canonical signaling pathway. After ligand binding, TGF-β receptors dimerize and phosphorylate intracellular SMAD proteins.Complex of SMAD2 and/or SMAD3 becomes phosphorylated by TβRI and forms a complex with SMAD4 which is subsequently transported intothe nucleus where it binds with specific transcription factors (TF) and induces a transcription of TGF-β dependent genes.
Figure 3 TGF-β non-canonical signaling pathway. After ligand binding, several different branching signaling pathways can be activated inmalignant cells, such as Notch signaling, MAP kinases, AKT/PKB pathway, GTP-binding proteins pathway, PTK pathway, NF-κB and Wnt/β-cateninpathway.
Figure 4 Role of TGF-β in regulation of cell cycle. Physiologically, TGF-β is a potent inhibitor of cell cycle; it induces expression of p15INK4Band represses expression of c-Myc
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