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. Author manuscript; available in PMC: 2013 Nov 9.
Published in final edited form as: Cancer Biol Ther. 2009 Sep;8(18):1691–1698. doi: 10.4161/cbt.8.18.9843

Figure 3.

Figure 3

TGF ligands signal through distinct receptors and Smads that are modulated by adaptor proteins and ubiquitinators. TGF binds to serine threonine kinase receptor complexes that phosphorylate R-Smads (Smad2/Smad3) as well as adaptor proteins such as 2-spectrin (2SP). R-Smads, 2-spectrin and Smad4 form a heteromeric complex, and translocate to the nucleus, activating target genes. At all levels, Smad modulation occurs through adaptor proteins as well as E3 ligases such as PRAJA and Smurfs, generating the diverse and complex signals. Arrows indicate signal flow and are color coded: black for ligand and receptor activation, red for Smad and receptor activation, olive green for Smad and receptor inactivation and formation of a transcriptional complex, and blue for Smad nucleocytoplasmic shuttling. Phosphate groups and ubiquitin (Ub) are represented by red stars and dark red circles, respectively.