Calcium integrin-binding protein activates platelet integrin αIIbβ3
Calcium integrin-binding protein activates platelet integrin αIIbβ3
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DOI：
10.1074/jbc.m110643200
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发表时间：
2002-01-18
影响因子：
4.8
通讯作者：
Tsuboi, S
中科院分区：
文献类型：
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作者：
Tsuboi, S
α（IIb）β（3）是血小板特异性整合素，在血小板聚集中起关键作用。α（IIb）β（3）与其配体（如纤维蛋白原和血管性血友病因子）的亲和力在一个未表征的细胞内过程（称为由内向外信号传导）中受到严格调节。钙整联蛋白结合蛋白（CIB）已被鉴定为与α（IIb）β（3）的α（IIb）亚基的胞质尾区相互作用的蛋白质，但其生理作用尚未确定。在本研究中，我证明CIB激活α（IIb）β（3）在体外和体内。CIB直接与α（IIb）胞质尾区相互作用，从而在体外纤维蛋白原结合测定中增加α（IIb）β（3）对纤维蛋白原的亲和力。CIB与α（IIb）胞质尾区的相互作用以Ca2+依赖的方式增强。生理激动剂ADP刺激血小板，激活α（IIb）β（3）。当CIB与α（IIb）胞质尾区的相互作用在天然血小板中被可渗透的竞争肽阻断时，即使在ADP存在下也检测不到α（IIb）β（3）活化。该结果表明CIB与α（IIb）胞质尾区的直接相互作用将α（IIb）β（3）从静止构象转化为活性构象。这表明CIB在调节α（IIb）β（3）对其配体的亲和力的途径之一中起着重要作用。
alpha(IIb)beta(3), a platelet-specific integrin, plays a critical role in platelet aggregation. The affinity of alpha(IIb)beta(3) for its ligands such as fibrinogen and von Willebrand factor is tightly regulated in an uncharacterized intracellular process termed inside-out signaling. Calcium integrin-binding protein (CIB) has been identified as a protein interacting with the cytoplasmic tail of the alpha(IIb) subunit Of alpha(IIb)beta(3), but its physiological role has not been defined. In the present study, I demonstrate that CIB activates alpha(IIb)beta(3) both in vitro and in vivo. CIB interacts directly with the alpha(IIb) cytoplasmic tail, thereby increasing the affinity of alpha(IIb)beta(3) for fibrinogen in an in vitro fibrinogen-binding assay. The interaction of CIB with the alpha(IIb) cytoplasmic tail is enhanced in a Ca2+-dependent manner. A physiological agonist, ADP, stimulates platelets, activating alpha(IIb)beta(3). When the interaction of CIB with the alpha(IIb) cytoplasmic tail is blocked in native platelets by a permeable competing peptide, alpha(IIb)beta(3) activation is not detected even in the presence of ADP. This result indicates that direct interaction of CIB with the alpha(IIb) cytoplasmic tail converts alpha(IIb)beta(3) from a resting to an active conformation. This suggests that CIB plays an important role in one of the pathways that modulate the affinity of alpha(IIb)beta(3) for its ligand.