Figure 2.

Schematic diagram of general and gene-specific transforming growth factor (TGF)β signaling in fibroblasts. TGFβ binds to the TGFβ type I and type II receptors, activates Smad3, which activates target gene expression by binding the sequence CAGA. This pathway regulates virtually every TGFβ responsive gene in fibroblasts. Conversely, TGFβ can act with endothelin-1 (ET-1), connective tissue growth factor (CTGF) and extra domain A-fibronectin (EDA-FN) via the endothelin receptor A and B (ETA/B) receptors, syndecan 4 and integrins to activate ERK and focal adhesion kinase (FAK), which are required for target gene expression, in a promoter-specific fashion (for details see text).