Activating mechanisms of platelet GPIIb-IIIa complex by the interaction of intracellular proteins

点击翻译按钮获取中文摘要

In order to determine the activating mechanisms of platelet GPIIb-IIIa complex, the role of several associated proteins was analyzed. β3-endonexin activated GPIIb-IIIa complex. However it did not effectively localize near the plasma membrane since it was a nuclear protein. CD98 activated GPIIb-IIIa complex during platelet and cell adhesion. IAP strongly activated GPIIb-IIIa complex and induced soluble ligand bindings only when it interacted with C-terminal domain of thrombospondin. Several cytoskeletal proteins including talin and filamin influenced the function of GPIIb-IIIa complex. To know these downstream pathways, proteins that bind to filamins were identified by yeast two hybrid screening. One clone was a novel cDNA, which encoded 375 amino acids and 45kDa protein. Deduced amino acid sequence showed that it contained a proline-rich domain at its N-terminal half and two LIM domains at C-terminus. We therefore, named it as FBLP-1 (Filamin Binding LIM Protein-1). Subcellular localization analysis showed that FBLP-1 co-localized with stress fibers, which stretched from focal adhesions containing GPIIb-IIIa complex. The cells, which over expressed FBLP-1, spread more effectively than the cells which did not express FBLP-1, suggesting that FBLP-1 plays a significant role on platelet adhesion. Further investigation of these associated proteins would clarify the activating mechanisms of platelet GPIIb-IIIa complex.