The annexin A2/S100A10 system in health and disease: emerging paradigms.
The annexin A2/S100A10 system in health and disease: emerging paradigms.
复制标题
DOI：
10.1155/2012/406273
复制
发表时间：
2012
影响因子：
--
通讯作者：
Hajjar KA
中科院分区：
文献类型：
--
作者：
Hedhli N;Falcone DJ;Huang B;Cesarman-Maus G;Kraemer R;Zhai H;Tsirka SE;Santambrogio L;Hajjar KA
自从三十多年前发现它作为src激酶底物以来，对膜联蛋白A2及其相关蛋白的生理功能的认识急剧增加。与其结合伴侣S100 A10（p11），A2形成细胞表面复合物，调节主要纤溶蛋白酶，纤溶酶的产生，并在止血和血栓形成的设置中动态调节。此外，该复合物在缺氧中转录上调，并促进组织如视网膜中的病理性新血管生成。在啮齿动物和人类癌症的例子中已经报道了A2和p11的失调。在细胞内，A2在关节炎后骨质溶解的内体修复中起关键作用，而细胞内p11调节精神性情绪障碍中5-羟色胺受体的活性。在人体研究中，A2系统导致急性早幼粒细胞白血病的凝血障碍，并且是抗磷脂综合征、脑血栓形成和可能的先兆子痫患者中高滴度自身抗体的靶点。人类ANXA 2基因的多态性与中风和缺血性骨坏死有关，这是镰状细胞病的两种严重并发症。总之，这些新发现表明，操纵膜联蛋白A2/S100 A10系统可能为治疗一系列人类疾病提供有希望的新途径。
Since its discovery as a src kinase substrate more than three decades ago, appreciation for the physiologic functions of annexin A2 and its associated proteins has increased dramatically. With its binding partner S100A10 (p11), A2 forms a cell surface complex that regulates generation of the primary fibrinolytic protease, plasmin, and is dynamically regulated in settings of hemostasis and thrombosis. In addition, the complex is transcriptionally upregulated in hypoxia and promotes pathologic neoangiogenesis in the tissues such as the retina. Dysregulation of both A2 and p11 has been reported in examples of rodent and human cancer. Intracellularly, A2 plays a critical role in endosomal repair in postarthroplastic osteolysis, and intracellular p11 regulates serotonin receptor activity in psychiatric mood disorders. In human studies, the A2 system contributes to the coagulopathy of acute promyelocytic leukemia, and is a target of high-titer autoantibodies in patients with antiphospholipid syndrome, cerebral thrombosis, and possibly preeclampsia. Polymorphisms in the human ANXA2 gene have been associated with stroke and avascular osteonecrosis of bone, two severe complications of sickle cell disease. Together, these new findings suggest that manipulation of the annexin A2/S100A10 system may offer promising new avenues for treatment of a spectrum of human disorders.
登录
查看更多内容
影响因子：
20.3
作者：
Das, Riku;Burke, Tim;Plow, Edward F.
通讯作者：
Plow, Edward F.
影响因子：
37.3
作者：
Banerjee, Abhijit G;Liu, Jie;Vishwanatha, Jamboor K
通讯作者：
Vishwanatha, Jamboor K
影响因子：
17.1
作者：
Alexander B;Warner-Schmidt J;Eriksson T;Tamminga C;Arango-Lievano M;Ghose S;Vernov M;Stavarache M;Musatov S;Flajolet M;Svenningsson P;Greengard P;Kaplitt MG
通讯作者：
Kaplitt MG
影响因子：
4.8
作者：
Deora, AB;Kreitzer, G;Hajjar, KA
通讯作者：
Hajjar, KA
影响因子：
4.8
作者：
Donier, E;Rugiero, F;Wood, JN
通讯作者：
Wood, JN