Btk is required for activation of Akt, PKC, and ERK1/2 in platelets stimulated by bt/VWF. In contrast to the results obtained using WT platelets, (A) phosphorylation of Akt was greatly diminished in Btk^xid/Y platelets treated by bt/VWF, (B) PKC was not activated in Btk^xid/Y platelets stimulated by bt/VWF (this assay demonstrates PKC activity by movement of a phosphorylated peptide substrate toward the positive electrode), and (C) ERK1/2 was not phosphorylated in Btk^xid/Y platelets stimulated by bt/VWF.