Nuclear Focal Adhesion Kinase.
Nuclear Focal Adhesion Kinase.
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核焦点粘附激酶。
DOI：
10.1161/circresaha.119.315395
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发表时间：
2019
影响因子：
20.1
通讯作者：
Weiser-Evans,MaryCM
中科院分区：
文献类型：
--
作者：
Lu,Sizhao;Weiser-Evans,MaryCM
168 Circulation Research 2019年7月5日定位于富含整合素的粘着斑部位。已知介导整联蛋白和生长因子信号传导途径以调节SMC增殖和运动。重要的是，SMC特异性FAK耗竭可抑制损伤诱导的新生内膜形成，支持其在促进病理性血管重塑中的作用。12 FAK是一种125 kDa的蛋白质，由促进其蛋白质支架功能的N-末端FERM结构域、中央激酶结构域、富含脯氨酸的区域和促进FAK定位于粘着斑的C-末端粘着斑靶向（FAT）结构域组成。11先前的研究确定了FAK的内源性抑制剂FRNK（FAK相关非激酶）作为FAK活性的SMC特异性调节剂。13 FRNK作为含有C-末端FAT结构域但缺乏激酶活性的独立蛋白质表达。FRNK通过与粘着斑中的FAK结合伴侣竞争性相互作用或通过将FAK的负调节剂募集到粘着斑复合物来抑制FAK活性。因此，这些早期的数据揭示了一种新的，内源性的，SMC特异性的机制来调节整合素和生长因子介导的FAK激活和SMC功能。目前的研究强调了FAK调节的一种新的内源性机制，将FAK作为病理性血管重塑的重要调节剂和治疗血管疾病的潜在新治疗靶点。
168 Circulation Research July 5, 2019 localizes to integrin-rich focal adhesion sites. 11 It is known to mediate integrin and growth factor signaling pathways to regulate SMC proliferation and motility. Importantly, SMC-specific depletion of FAK was shown to inhibit injury-induced neointima formation supporting its role in facilitating pathological vascular remodeling. 12 FAK is a 125-kDa protein that consists of an N-terminal FERM domain that facilitates its protein scaffolding function, a central kinase domain, proline-rich regions, and a C-terminal focal adhesion targeting (FAT) domain that promotes localization of FAK to focal adhesions. 11 Previous studies identified an endogenous inhibitor of FAK, FRNK (FAK-related nonkinase), as a SMC-specific regulator of FAK activity. 13 FRNK is expressed as an independent protein containing the C-terminal FAT domain but lacking kinase activity. FRNK inhibits FAK activity by competitively interacting with FAK binding partners in focal adhesions or through recruitment of negative regulators of FAK to focal complexes. Thus, these earlier data revealed a novel, endogenous, and SMC-specific mechanism in place to regulate integrin-and growth factor-mediated FAK activation and SMC function. The current study highlights a new endogenous mechanism of FAK regulation, placing FAK as an essential regulator of pathological vascular remodeling and a potential novel therapeutic target for the treatment of vascular disease.
影响因子：
16
作者：
Lim, Ssang-Taek;Chen, Xiao Lei;Llic, Dusko
通讯作者：
Llic, Dusko
影响因子：
20.1
作者：
Mano, T;Luo, ZY;Walsh, K
通讯作者：
Walsh, K