Regulation of ack-family nonreceptor tyrosine kinases.
Regulation of ack-family nonreceptor tyrosine kinases.
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DOI：
10.1155/2011/742372
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Miller WT
中科院分区：
文献类型：
--
作者：
Prieto-Echagüe V;Miller WT
Ack家族非受体酪氨酸激酶在结构域组成和调节特性方面是独特的。人Ack 1（活化Cdc 42相关激酶）广泛表达，并被包括生长因子和整合素介导的细胞粘附在内的信号激活。刺激导致Ack 1自身磷酸化和C-末端中额外残基的磷酸化。N-末端SAM结构域是完全激活所必需的。Ack 1通过蛋白质-蛋白质相互作用发挥其某些作用，而这些作用与其激酶活性无关。在基础状态下，Ack 1活性被催化结构域和C-末端区域之间的分子内相互作用抑制。不适当的Ack 1激活和信号转导与几种癌症的发展、进展和转移有关。因此，有越来越多的兴趣在Ack 1作为药物靶点，和酶的调节特性的研究可能会揭示的功能，可以利用抑制剂的设计。
Ack family non-receptor tyrosine kinases are unique with regard to their domain composition and regulatory properties. Human Ack1 (activated Cdc42-associated kinase) is ubiquitously expressed and is activated by signals that include growth factors and integrin-mediated cell adhesion. Stimulation leads to Ack1 autophosphorylation and to phosphorylation of additional residues in the C-terminus. The N-terminal SAM domain is required for full activation. Ack1 exerts some of its effects via protein-protein interactions that are independent of its kinase activity. In the basal state, Ack1 activity is suppressed by an intramolecular interaction between the catalytic domain and the C-terminal region. Inappropriate Ack1 activation and signaling has been implicated in the development, progression, and metastasis of several forms of cancer. Thus, there is increasing interest in Ack1 as a drug target, and studies of the regulatory properties of the enzyme may reveal features that can be exploited in inhibitor design.