Human Immunodeficiency Virus Type 1 Nef Selectively Associates with a Catalytically Active Subpopulation of p21-Activated Kinase 2 (PAK2) Independently of PAK2 Binding to Nck or β-PIX
Human Immunodeficiency Virus Type 1 Nef Selectively Associates with a Catalytically Active Subpopulation of p21-Activated Kinase 2 (PAK2) Independently of PAK2 Binding to Nck or β-PIX
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人类免疫缺陷病毒 1 型 Nef 选择性地与 p21 激活激酶 2 (PAK2) 的催化活性亚群相关，独立于 PAK2 与 Nck 或 β-PIX 的结合
DOI：
10.1128/jvi.75.5.2154-2160.2001
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发表时间：
2001
影响因子：
5.4
通讯作者：
K. Saksela
中科院分区：
文献类型：
--
作者：
G. Renkema;A. Manninen;K. Saksela
摘要我们最近发现Nef相关的丝氨酸苏氨酸激酶(NAK)是p21激活的蛋白2(PAK2)。在这里，我们利用了通过转染PAK2 cDNA或其突变的衍生物来操纵NAK的功能性质的可能性，以便进一步表征Nef-NAK复合体。为了排除某些Nef变异体可能与PAK1而不是PAK2相互作用的可能性，我们还研究了NAK与不同的人类免疫缺陷病毒1型HIV-1Nef蛋白的复合体的特性。所有被测试的Nef蛋白，包括SF2、NL4-3、BH10和HAN-2，都与PAK2相关，而不与PAK1相关。通过在这两个PAK蛋白之间交换不同的区域，PAK2与Nef结合的选择性可以被映射到其调节域的羧基末端部分。PAK2与适配蛋白NCK或β-PIX的结合对于Nef-PAK2复合体的组装是必不可少的，而完整的Cdc42-rac1相互作用结合基序是必需的。最重要的是，我们发现NAK代表了细胞总PAK2中一个独特的亚群，其特征是具有高特异性的激酶活性。因此，虽然只有一小部分细胞PAK2与Nef形成复合体，但NAK代表了细胞PAK2活性的主要部分。
ABSTRACT We have recently identified the Nef-associated serine-threonine kinase (NAK) as the p21-activated kinase 2 (PAK2). Here we have taken advantage of the possibility to manipulate the functional properties of NAK by transfecting PAK2 cDNA or its mutant derivatives in order to further characterize the Nef-NAK complex. To exclude the possibility that some Nef variants might interact with PAK1 instead of PAK2, we also examined the identity of NAK complexed with divergent human immunodeficiency virus type 1 HIV-1 Nef proteins. All tested Nef proteins, including SF2, NL4-3, BH10, and HAN-2, associated with PAK2 but not with PAK1. By exchanging different regions between these two PAK proteins, the selective ability of PAK2 to associate with Nef could be mapped to the carboxy-terminal part of its regulatory domain. Binding of PAK2 with the adapter protein Nck or β-PIX was found to be dispensable for the assembly of the Nef-PAK2 complex, whereas an intact Cdc42-Rac1 interactive binding motif was required. Most importantly, we found that NAK represented a distinct subpopulation of the total cellular PAK2 characterized by a high specific kinase activity. Thus, although only a small fraction of cellular PAK2 could be found in complex with Nef, NAK represented a major part of cellular PAK2 activity.
HIV-1 Nef 与细胞丝氨酸激酶的关联与增强的病毒粒子感染性和有效的前病毒 DNA 合成相关。
影响因子：
3.7
作者：
Wiskerchen,M;Cheng-Mayer,C
通讯作者：
Cheng-Mayer,C
影响因子：
56.9
作者：
Rudel, T;Bokoch, GM
通讯作者：
Bokoch, GM