Figure 3. FAK signals increase FGFR surface expression and inhibit SMA expression. Numbers indicate sequential steps in the signaling scheme. TGFß induces myofibroblast differentiation and increases expression of integrins and fibronectin (step 1). Fibronectin binding to integrins activates FAK (step 2). FAK activation leads to increased cell-surface expression of FGFRs by increased retention of FGFR in the cell membrane and/or by increased FGFR gene expression (step 3). Increased cell-surface expression of FGFRs transmits FGF signals and increases activation of the FGF pathway via FRS2/ERK (step 4), which negatively regulate the levels of SMA (step 5). TGFßr, TGFß receptor; FGFR, FGF receptor; HSPG, heparin sulfate proteoglycan; G, Grb2; S, Sos.