ABL tyrosine kinases: evolution of function, regulation, and specificity.
ABL tyrosine kinases: evolution of function, regulation, and specificity.
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DOI：
10.1126/scisignal.3139re6
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发表时间：
2010-09-14
影响因子：
7.3
通讯作者：
Colicelli J
中科院分区：
文献类型：
--
作者：
Colicelli J
ABL家族蛋白质包括酪氨酸激酶的最保守分支之一。每个ABL蛋白含有SH 3-SH 2-TK（Src同源3-Src同源2-酪氨酸激酶）结构域盒，其赋予自调节激酶活性并且在非受体酪氨酸激酶中是常见的。该盒被耦合到肌动蛋白结合和捆绑域，这使得ABL蛋白能够连接磷酸化调节与肌动蛋白丝重组。两种脊椎动物旁系同源基因ABL 1和ABL 2已经进化到执行专门的功能。ABL 1包括核定位信号和DNA结合结构域，通过它介导DNA损伤修复功能，而ABL 2具有额外的肌动蛋白和微管结合能力，以增强其细胞骨架重塑功能。几种类型的翻译后修饰控制ABL催化活性，亚细胞定位和稳定性，与细胞质和核ABL功能的后果。结合伴侣提供ABL催化活性、底物特异性和下游信号传导的额外调节。关于ABL调节机制的信息正在被挖掘，以提供新的治疗策略，对BCR-ABL 1和相关的致白血病蛋白引起的造血系统恶性肿瘤。
ABL-family proteins comprise one of the best conserved branches of the tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3–Src homology 2–tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. This cassette is coupled to an actin-binding and -bundling domain, which makes ABL proteins capable of connecting phosphoregulation with actin-filament reorganization. Two vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain through which it mediates DNA damage-repair functions, whereas ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. Information on ABL regulatory mechanisms is being mined to provide new therapeutic strategies against hematopoietic malignancies caused by BCR-ABL1 and related leukemogenic proteins.
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影响因子：
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