Molecular Crosstalk between Integrins and Cadherins: Do Reactive Oxygen Species Set the Talk?

Figure 2

ROS mediate integrin outside-in signaling. Integrin engagement with extracellular matrix (ECM) proteins triggers a transient and localized burst of ROS, either independently or in cooperation with growth factor receptors (GFR), which is essential to the proper transduction of outside-in signaling pathways. The small GTPase Rac1 acts as a crucial upstream regulator of ROS production, orchestrating integrin outside-in signaling-mediated changes in mitochondrial metabolic/redox function, and activation of distinct oxidases, including NADPH-oxidases (NOX), 5-lipoxygenase (5-LOX), and cyclooxygenase-2 (COX-2). The signaling properties of integrin-induced ROS are largely due to the reversible oxidation of specific subsets of redox-sensitive proteins, including oxidative inhibition of PTPs, and activation of PTKs, RPTKs, small GTPases of the Ras and Rho families, and transcription factors (TF) such as AP-1 and NF-κB.