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. Author manuscript; available in PMC: 2010 Jan 25.
Published in final edited form as: Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3450–3460. doi: 10.1167/iovs.05-1208

FIGURE 14.

FIGURE 14

TGF-β induced Smad-dependent and -independent signaling pathways. On ligand binding, type I and type II receptors are activated, and phosphorylation of R-Smads (Smad2/3) occurs. Phosphorylated R-Smads form heterotrimeric complexes with co-Smad (Smad 4) and translocate to the nucleus. The Smad complexes interact with other transcription factors (TF) at DNA sequence-specific binding sites (transcription factor binding element [TBE] Smad binding element [SBE]) to regulate gene expression. Smad7 is an inhibitory Smad that prevents receptor activation of R-Smads. Smad3 phosphorylation is prevented in Smad3-null mice, and so TGF-β-induced responses are presumed to occur through activation of other TGF-β-induced signaling pathways. TGF-β also induces activation of the MAPK pathways (JNK, p38 and ERK1, 2) through the upstream mediators RhoA, Ras, and TAK1. Additional pathways involving PI3K have been shown to mediate EMT. Modified with permission from Roberts AB, Derynck R. Meeting Report: Signaling Schemes for TGF-β. Sci. STKE 2001;pe43. http://stke.sciencemag.org/cgi/content/full/OC sigtrans;2001/113/pe43. © 2001 AAAS.