The 14-3-3zeta-GPIb-IX-V complex as an antiplatelet target

The functional nexus involving the platelet adhesion receptor, the glycoprotein (GP)Ib-IX-V complex, and the signaling protein, 14-3-3zeta, is emerging as a new drug target for control of GPIb-IX-V-dependent thrombotic diseases such as heart attack and stroke. Together, advances in understanding mechanisms of regulation and functional consequences of the GPIb-IX-V/14-3-3zeta interaction, and the growing potential of 14-3-3-targeting therapeutic approaches used for 14-3-3-dependent processes in other cells--principally involving cell cycling and cancer--point to 14-3-3zeta as a promising antithrombotic target. The unique recognition sequences and arrangement of functional 14-3-3zeta-binding sites found within the cytoplasmic domain of GPIb-IX-V increase the likelihood of selective targeting of this interaction.