Analysis of signaling pathways implicated in agonist-induced glycoprotein shedding. Washed platelets were pretreated with ADAM10/17 GW280264X, the calpain inhibitor MDL-28170, the pan-caspase inhibitor Q-VD-OPh, the general PKC inhibitor Ro-318425, the Ca²⁺ chelator dm-BAPTA AM, or the Ca²⁺ entry inhibitor 2APB. Samples were stimulated with ionomycin/CaCl₂, CRP-XL plus thrombin, PMA, ABT-737, or CCCP, as indicated. Data are normalized to those of unstimulated platelets without any inhibitors. Shown is a heat map representing the effects of agonists on GPIbα shedding (red), as well as relative antagonizing effects of inhibitors (blue). Note the 3 clusters representing a role for Ca²⁺ elevation (i), caspase activation (ii), and PKC activity (iii). See supplemental Table 1 for additional information.