Figure 2: VCAM-1 and ICAM-1 signal transduction. A) Crosslinking of VCAM-1 activates calcium fluxes and Rac-1 which then activates endothelial cell NOX2. NOX2 catalyzes the production of superoxide that then dismutates to H2O2. VCAM-1 induces the production of only 1 μM H2O2. Within minutes of its production, H2O2 activates endothelial cell-associated matrix metalloproteinases (MMPs) that degrade extracellular matrix and endothelial cell surface receptors in cell junctions. H2O2 also diffuses through membranes at 100 μm/sec to oxidize and transiently activate endothelial cell protein kinase C-α (PKCα). PKCα phosphorylates and activates protein tyrosine phosphatase 1B (PTP1B). PTP1B is not oxidized. These signals through reactive oxygen species (ROS), MMPs, PKCα, and PTP1B are required for VCAM-1-dependent leukocyte transendothelial migration. B) ICAM-1 activates XO, PLC, and ERK1/2 which then activates PKCα. PKCα is not oxidized during ICAM-1 signaling in endothelial cells.