Figure 1.

TGFβ signaling pathway. Following the release from the large latent complex (LLP), TGFβ dimers binds to the heteromeric TGFβ receptor, which consists of type I and type II receptors (such as TGFβRI and TGFβII). Within canonical signaling, this results in receptor phosphorylation with the subsequent activation of the receptor activated SMAD molecules (R-SMADs), such as SMAD2 or SMAD3. Phosphorylated R-SMADs form a heteromeric complex with SMAD4, which translocates to the nucleus and induces the transcription of target genes. Inhibitory SMADs (I-SMADs) such as SMAD7 can inhibit TGFβ signaling at several points. In non-canonical TGFβ signaling, TGFβ receptor activation results in the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), phosphatidylinositol-3 kinase (PI3K)/Akt, TGFβ-activated kinase-1 (TAK1) pathways, and others. The figure has been adapted from [9].