Figure 3.

Transforming growth factor beta signaling pathway TGFβ1 latent proteins are present in 2 forms; a small complex consists of TGF-β noncovalently associated with a latency-associated protein (LAP) and a large latent complex in which LAP is linked to latent TGF-β-binding proteins (LTBPs). Integrins, plasmin and thrombospondin 1 (TSP-1) convert the inactive latent complex to the active form by releasing it from LTBP and LAP. The active TGF-β I binds to the type II receptor (TRII) which then recruits, transphosphorylates and binds the type I receptor (TRI). The activated TRI phosphorylates the transcription factors R-Smads (Smad 2/3) which then bind to the common Smad 4. R-Smad/Co-Smad complexes translocate to the nucleus, where they associate with DNA-binding partners and then regulate the transcriptional response of the TGF- β target genes. Inhibitory Smad 6 and 7 repress TGF-β responses.