Myelin protein zero/P0 phosphorylation and function require an adaptor protein linking it to RACK1 and PKC alpha.
Myelin protein zero/P0 phosphorylation and function require an adaptor protein linking it to RACK1 and PKC alpha.
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DOI：
10.1083/jcb.200608060
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发表时间：
2007-05-21
影响因子：
7.8
通讯作者：
Balsamo, Janne
中科院分区：
文献类型：
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作者：
Gaboreanu, Ana-Maria;Hrstka, Ronald;Xu, Wenbo;Shy, Michael;Kamholz, John;Lilien, Jack;Balsamo, Janne
髓鞘蛋白零（P0;外周神经系统中的主要髓鞘蛋白）胞质结构域的点突变改变了蛋白激酶Cα（PKCα）底物基序（198 HRSTK 201）或改变了丝氨酸199和/或204，消除了P0介导的粘附。PKCα底物基序（R198 S）的突变也会导致一种遗传性周围神经病变（Charcot玛丽牙病[CMT] 1B），表明PKCα介导的P0磷酸化对髓鞘形成很重要。我们现在已经确定了一个65 kD的衔接蛋白，连接P0与活化C激酶1（RACK 1）的受体。p65与P0的相互作用映射到P0的胞质尾内的残基179-197。破坏p65结合的突变或缺失减少了P0磷酸化和粘附，这可以通过用谷氨酸取代丝氨酸199和204来挽救。两个CMT家系的p65结合序列G184 R发生突变，该残基的突变导致p65结合和粘附功能的丧失。
Point mutations in the cytoplasmic domain of myelin protein zero (P0; the major myelin protein in the peripheral nervous system) that alter a protein kinase Cα (PKCα) substrate motif (198HRSTK201) or alter serines 199 and/or 204 eliminate P0-mediated adhesion. Mutation in the PKCα substrate motif (R198S) also causes a form of inherited peripheral neuropathy (Charcot Marie Tooth disease [CMT] 1B), indicating that PKCα-mediated phosphorylation of P0 is important for myelination. We have now identified a 65-kD adaptor protein that links P0 with the receptor for activated C kinase 1 (RACK1). The interaction of p65 with P0 maps to residues 179–197 within the cytoplasmic tail of P0. Mutations or deletions that abolish p65 binding reduce P0 phosphorylation and adhesion, which can be rescued by the substitution of serines 199 and 204 with glutamic acid. A mutation in the p65-binding sequence G184R occurs in two families with CMT, and mutation of this residue results in the loss of both p65 binding and adhesion function.