Neurofilament tail phosphorylation: identity of the RT-97 phosphoepitope and regulation in neurons by cross-talk among proline-directed kinases.
Neurofilament tail phosphorylation: identity of the RT-97 phosphoepitope and regulation in neurons by cross-talk among proline-directed kinases.
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DOI：
10.1111/j.1471-4159.2008.05547.x
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发表时间：
2008-10
影响因子：
4.7
通讯作者：
Nixon RA
中科院分区：
文献类型：
--
作者：
Veeranna;Lee JH;Pareek TK;Jaffee H;Boland B;Vinod KY;Amin N;Kulkarni AB;Pant HC;Nixon RA
随着轴突髓鞘形成，建立稳定的神经丝网络，并扩大口径，神经丝蛋白质被广泛磷酸化沿着其C-末端尾巴，这是识别的单克隆抗体，RT-97。在这里，我们证明在体内RT-97 immunureactivity是由磷酸化KSPXK或KSPXXXK基序，并需要侧翼赖氨酸在特定的位置。ERK 1，2和pERK 1，2水平的增加与RT-97表位的磷酸化平行，在出生后的大脑发育早期。纯化的ERK 1，2在重组NF-H尾域蛋白上的两个KSP基序上产生RT-97，而cdk 5仅磷酸化KSPXK基序。原代海马神经元中RT-97表位的产生受到ERK 1，2，JNK 1，2和cdk 5之间广泛串扰的调节。ERK 1，2和JNK 1，2的抑制完全阻断RT-97的产生。Cdk 5通过调节JNK的活化间接影响RT-97的产生。在小鼠中，cdk 5基因缺失没有显著改变RT-97 IR或ERK 1，2和JNK活化。在缺乏cdk 5激活剂P35的小鼠中，cdk 5活性的部分抑制通过激活ERK 1，2增加RT-97 IR。因此，cdk 5影响RT-97表位的产生，部分通过调节ERK和JNK，这是两个主要的激酶调节神经丝磷酸化。多个蛋白激酶对单个靶点的调节强调了当特定蛋白激酶的活性被阻断时监测其他相关激酶的重要性。
As axons myelinate, establish a stable neurofilament network, and expand in caliber, neurofilament proteins are extensively phosphorylated along their C-terminal tails, which is recognized by the monoclonal antibody, RT-97. Here, we demonstrate in vivo that RT-97 immunureactivity is generated by phosphorylation at KSPXK or KSPXXXK motifs and requires flanking lysines at specific positions. ERK1,2 and pERK1,2 levels increase in parallel with phosphorylation at the RT-97 epitope during early post-natal brain development. Purified ERK1,2 generated RT-97 on both KSP motifs on recombinant NF-H tail domain proteins, while cdk5 phosphorylated only KSPXK motifs. RT-97 epitope generation in primary hippocampal neurons was regulated by extensive crosstalk among ERK1,2, JNK1,2 and cdk5. Inhibition of both ERK1,2 and JNK1,2 completely blocked RT-97 generation. Cdk5 influenced RT-97 generation indirectly by modulating JNK activation. In mice, cdk5 gene deletion did not significantly alter RT-97 IR or ERK1,2 and JNK activation. In mice lacking the cdk5 activator P35, the partial suppression of cdk5 activity increased RT-97 IR by activating ERK1,2. Thus, cdk5 influences RT-97 epitope generation partly by modulating ERKs and JNKs, which are the two principal kinases regulating neurofilament phosphorylation. The regulation of a single target by multiple protein kinases underscores the importance of monitoring other relevant kinases when the activity of a particular one is blocked.
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DOI：
10.1073/pnas.100460897
发表时间：
2000-05-23
影响因子：
11.1
作者：
Huang, KX;Paudel, HK
通讯作者：
Paudel, HK
DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
2.5
作者：
LAWSON, SN;HARPER, AA;ANDERTON, BH
通讯作者：
ANDERTON, BH
影响因子：
4.8
作者：
Favata, MF;Horiuchi, KY;Trzaskos, JM
通讯作者：
Trzaskos, JM
影响因子：
4.7
作者：
COLEMAN, MP;ANDERTON, BH
通讯作者：
ANDERTON, BH