Calcium-dependent properties of CIB binding to the integrin αIIb cytoplasmic domain and translocation to the platelet cytoskeleton
Calcium-dependent properties of CIB binding to the integrin αIIb cytoplasmic domain and translocation to the platelet cytoskeleton
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DOI：
10.1042/0264-6021:3420729
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发表时间：
1999-09-15
影响因子：
4.1
通讯作者：
Parise, LV
中科院分区：
文献类型：
--
作者：
Shock, DD;Naik, UP;Parise, LV
α IIb β 3整合素在激动剂激活的血小板中接收信号，导致其转化为结合纤维蛋白原的活性构象，从而介导血小板聚集。纤维蛋白原结合α IIb β 3随后诱导细胞内级联信号事件。这种双向α IIb β 3介导的信号传导的分子机制尚不清楚，但可能涉及蛋白质与整合素细胞质结构域的结合。我们之前报道了一种新的22 kda，含有ef -手的蛋白质的序列，称为CIB（钙和整合素结合蛋白），在酵母-双杂交系统中与α IIb细胞质结构域特异性相互作用。对多种组织和细胞系的进一步分析表明，CIB mRNA和蛋白广泛表达。此外，等温滴定量热法表明，CIB以Ca2+依赖的方式与α IIb细胞质结构域肽结合，具有中等亲和力（K-d,: 700 nM）和1:1的化学计量。在聚集的血小板中，内源性CIB和α IIb β 3以平行方式转运到Triton x -100不溶性细胞骨架；表明CIB的细胞定位可能受到α IIb β 3的调节。因此，CIB可能通过Ca2+调节与α IIb细胞质结构域的结合和细胞内分布变化的机制参与整合素相关功能。
The alpha IIb beta 3 integrin receives signals in agonist-activated platelets, resulting in its conversion to an active conformation that binds fibrinogen, thereby mediating platelet aggregation. Fibrinogen binding to alpha IIb beta 3 subsequently induces a cascade of intracellular signalling events. The molecular mechanisms of this bi-directional alpha IIb beta 3-mediated signalling are unknown but may involve the binding of proteins to the integrin cytoplasmic domains. We reported previously the sequence of a novel 22-kDa, EF-hand-containing, protein termed CIB (calcium- and integrin-binding protein) that interacts specifically with the alpha IIb cytoplasmic domain in the yeast-two-hybrid system. Further analysis of numerous tissues and cell lines indicated that CIB mRNA and protein are: widely expressed. In addition, isothermal titration calorimetry indicated that CIB binds to an alpha IIb cytoplasmic-domain peptide in a Ca2+-dependent manner, with moderate affinity (K-d,: 700 nM) and 1:1 stoichiometry. In aggregated platelets, endogenous CIB and alpha IIb beta 3 translocate to the Triton X-100-insoluble cytoskeleton in a parallelmanner; demonstrating that the cellular localization of CIB is regulated, potentially by alpha IIb beta 3. Thus CIB may contribute to integrin-related functions by mechanisms involving Ca2+-modulated binding to the alpha IIb cytoplasmic domain and changes in intracellular distribution.