N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells
N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells
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DOI：
10.1042/bj20121201
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发表时间：
2013-02-01
影响因子：
4.1
通讯作者：
Kobayashi, Takayasu
中科院分区：
文献类型：
--
作者：
Chida, Toko;Ando, Masakatsu;Kobayashi, Takayasu
PPM[金属依赖性蛋白磷酸酶，以前称为PP2C（蛋白磷酸酶2C）]家族成员在调节各种信号通路中发挥重要作用。在寻找作用于AMPK （amp活化的蛋白激酶）的蛋白磷酸酶时，我们发现PPM1A和PPM1B是n -肉豆酰化的，这种修饰对于它们在细胞中去磷酸化AMPK的α亚基（AMPK α）的能力是必不可少的。细胞中PPM1A和PPM1B的另外两种功能也需要n -肉豆蔻酰化。虽然PPM1A和PPM1B的非肉豆芽酰化突变（G2A）阻止了膜结合，但这种重新定位不太可能导致对AMPK α的活性降低。在体外实验中，与野生型相比，G2A突变体对AMPK α的活性降低，但对人工底物PNPP（对硝基苯基磷酸）的特异性活性高得多。综上所述，本研究的结果表明，PPM1A和PPM1B的n -肉豆粕酰化在细胞对其生理底物的识别中起着关键作用。
PPM [metal-dependent protein phosphatase, formerly called PP2C (protein phosphatase 2C)] family members play essential roles in regulating a variety of signalling pathways. While searching for protein phosphatase(s) that act on AMPK (AMP-activated protein kinase), we found that PPM1A and PPM1B are N-myristoylated and that this modification is essential for their ability to dephosphorylate the alpha subunit of AMPK (AMPK alpha) in cells. N-Myristoylation was also required for two other functions of PPM1A and PPM1B in cells. Although a non-myristoylated mutation (G2A) of PPM1A and PPM1B prevented membrane association, this relocalization did not likely cause the decreased activity towards AMPK alpha. In in vitro experiments, the G2A mutants exhibited reduced activities towards AMPK alpha, but much higher specific activity against an artificial substrate, PNPP (p-nitrophenyl phosphate), compared with the wild-type counterparts. Taken together, the results of the present study suggest that N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells.