Btk is activated by platelet glycoprotein receptors and transmits signals to increase cytosolic calcium. The signaling pathways of platelet glycoprotein receptors that are coupled to Btk are depicted. Solid arrows indicate direct interaction, dashed arrows indicate indirect activation. The homologous kinase Tec is activated through the same pathways but plays a functional role only after GPVI activation. For details see text. CLEC-2, C-type lectin domain family 2; DAG, 1,2-diacylglycerol; FcγRIIa, Fc fragment of IgG low affinity IIa receptor; FcRγ, Fc receptor gamma-chain; GPVI, glycoprotein VI; GPIb-V-IX, glycoproteins Ib,V,IX; hemITAM, single-copy tyrosine-based activation motif; IP3, inositol 1,4,5 triphosphate; ITAM, immunoreceptor tyrosine-based activation motif; PLC2γ2, phospholipase Cγ2; PI3-kinase, phosphatidylinositol 3-kinase; PIP2, phosphatidylinositol(4,5)-bisphosphate; PIP3, phosphatidylinositol(3,4,5)-trisphosphate; SFK, Src family kinases; Syk, spleen tyrosine kinase, VWF, von Willebrand factor.