Selective Desensitization of Growth Factor Signaling by Cell Adhesion to Fibronectin*□S

Cell adhesion to the extracellular matrix is required to exe-cute growth factor (GF)-mediated cell behaviors, such as prolif-eration. A major underlying mechanism is that cell adhesion enhances GF-mediated intracellular signals, such as extracellu-lar signal-regulated kinase (Erk). However, because GFs use dis-tinct mechanisms to activate Ras-Erk signaling, it is unclear whether adhesion-mediated enhancement of Erk signaling is universal to all GFs. We examined this issue by quantifying the dynamics of Erk signaling induced by epidermal growth factor, basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) in NIH-3T3 fibroblasts. Adhesion to fibronectin-coated surfaces enhances Erk signaling elicited by epidermal growth factor but not by bFGF or PDGF. Unexpect-edly, adhesion is not always a positive influence onGF-mediated signaling. At critical subsaturating doses of PDGF or bFGF, cel