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.
Andrews
Robert K
RK
Department of Immunology, Monash University, Melbourne, Australia.
Du
Xiaoping
X
Berndt
Michael C
MC
D048948:14-3-3 Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects
D048948:14-3-3 Proteins; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex