Regulation of the Catalytic Activity of Herpes Simplex Virus 1 Protein Kinase Us3 by Autophosphorylation and Its Role in Pathogenesis
Regulation of the Catalytic Activity of Herpes Simplex Virus 1 Protein Kinase Us3 by Autophosphorylation and Its Role in Pathogenesis
复制标题
单纯疱疹病毒1蛋白激酶Us3自磷酸化催化活性的调节及其在发病机制中的作用
DOI：
10.1128/jvi.00103-09
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发表时间：
2009
影响因子：
5.4
通讯作者：
Y. Kawaguchi
中科院分区：
文献类型：
--
作者：
Ken Sagou;Takahiko Imai;H. Sagara;M. Uema;Y. Kawaguchi
Us 3是由单纯疱疹病毒1型（HSV-1）编码的一种丝氨酸/苏氨酸蛋白激酶。我们最近鉴定了Us 3第147位的丝氨酸（Ser-147）作为Us 3的生理磷酸化位点（A. Kato，M.田中，M。山本河，巴西-地Asai，T. Sata，Y. Nishiyama和Y.川口，J. Virol. 82：6172-6189，2008）。在本研究中，我们研究了Us 3 Ser-147磷酸化对感染细胞中Us 3催化活性的调节和对HSV-1发病机制的影响。我们的结果如下。(i)只有一小部分从感染的细胞纯化的Us 3在Ser-147磷酸化。(ii)从感染细胞中纯化的在Ser-147处磷酸化的Us 3具有比在Ser-147处未磷酸化的Us 3显著更高的激酶活性。(iii)感染细胞中Us 3 Ser-147的磷酸化依赖于Us 3激酶活性。(iv)用丙氨酸替换Us 3 Ser-147显著降低了小鼠角膜中的病毒复制以及小鼠中疱疹性基质角膜炎和眼周皮肤病的发展。这些结果表明，Us 3的催化活性是严格调节的Ser-147在感染的细胞中的自磷酸化和调节Us 3活性的自磷酸化似乎在体内病毒复制和HSV-1的发病机制中发挥了关键作用。
ABSTRACT Us3 is a serine/threonine protein kinase encoded by herpes simplex virus 1 (HSV-1). We recently identified serine at Us3 position 147 (Ser-147) as a physiological phosphorylation site of Us3 (A. Kato, M. Tanaka, M. Yamamoto, R. Asai, T. Sata, Y. Nishiyama, and Y. Kawaguchi, J. Virol. 82:6172-6189, 2008). In the present study, we investigated the effects of phosphorylation of Us3 Ser-147 on regulation of Us3 catalytic activity in infected cells and on HSV-1 pathogenesis. Our results were as follows. (i) Only a small fraction of Us3 purified from infected cells was phosphorylated at Ser-147. (ii) Us3 phosphorylated at Ser-147 purified from infected cells had significantly higher kinase activity than Us3 not phosphorylated at Ser-147. (iii) Phosphorylation of Us3 Ser-147 in infected cells was dependent on Us3 kinase activity. (iv) Replacement of Us3 Ser-147 by alanine significantly reduced viral replication in the mouse cornea and the development of herpes stromal keratitis and periocular skin disease in mice. These results indicated that Us3 catalytic activity is tightly regulated by autophosphorylation of Ser-147 in infected cells and that regulation of Us3 activity by autophosphorylation appeared to play a critical role in viral replication in vivo and in HSV-1 pathogenesis.
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DOI：
10.1073/pnas.98.4.1895
发表时间：
2001-02
影响因子：
11.1
作者：
D. Wolf;C. T. Courcelle;M. Prichard;E. Mocarski
通讯作者：
D. Wolf;C. T. Courcelle;M. Prichard;E. Mocarski
DOI：
10.1073/pnas.0503230102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Polcicova, K;Biswas, PS;Johnson, DC
通讯作者：
Johnson, DC
DOI：
10.1073/pnas.90.14.6701
发表时间：
1993-07-15
影响因子：
11.1
作者：
PURVES, FC;OGLE, WO;ROIZMAN, B
通讯作者：
ROIZMAN, B
影响因子：
3.7
作者：
Ogg, PD;McDonell, PJ;Roller, RJ
通讯作者：
Roller, RJ
DOI：
10.1073/pnas.0403160101
发表时间：
2004-06-22
影响因子：
11.1
作者：
Benetti, L;Roizman, B
通讯作者：
Roizman, B