Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
Protein phosphatase-1α interacts with and dephosphorylates polycystin-1.
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DOI：
10.1371/journal.pone.0036798
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Calvet JP
中科院分区：
文献类型：
--
作者：
Parnell SC;Puri S;Wallace DP;Calvet JP
多囊蛋白信号可能受磷酸化调节。虽然许多潜在的蛋白激酶和它们的多囊蛋白-1上的靶磷酸化位点已经被鉴定，但相应的磷酸酶尚未被广泛研究。我们已经确定多囊蛋白-1是蛋白磷酸酶-1 α（PP 1 α）的调节亚基。序列分析揭示了在多囊蛋白-1的胞质C-末端尾部存在高度保守的PP 1相互作用基序;我们已经表明，转染的PP 1 α特异性地与多囊蛋白-1的C-尾部结构共免疫沉淀。为了确定PP 1 α是否使多囊蛋白-1去磷酸化，PKA磷酸化GST-多囊蛋白-1融合蛋白被PP 1 α去磷酸化，但不被PP 2B（钙调磷酸酶）去磷酸化。多囊蛋白-1的PP 1结合基序内的突变，包括常染色体显性遗传性多囊肾病（ADPKD）相关突变，可显著降低PP 1 α介导的多囊蛋白-1去磷酸化。结果表明，多囊蛋白-1通过多囊蛋白-1 C-尾内保守的PP 1结合基序与PP 1 α形成全酶复合物，并且PKA磷酸化的多囊蛋白-1作为全酶的底物。
Polycystin signaling is likely to be regulated by phosphorylation. While a number of potential protein kinases and their target phosphorylation sites on polycystin-1 have been identified, the corresponding phosphatases have not been extensively studied. We have now determined that polycystin-1 is a regulatory subunit for protein phosphatase-1α (PP1α). Sequence analysis has revealed the presence of a highly conserved PP1-interaction motif in the cytosolic, C-terminal tail of polycystin-1; and we have shown that transfected PP1α specifically co-immunoprecipitates with a polycystin-1 C-tail construct. To determine whether PP1α dephosphorylates polycystin-1, a PKA-phosphorylated GST-polycystin-1 fusion protein was shown to be dephosphorylated by PP1α but not by PP2B (calcineurin). Mutations within the PP1-binding motif of polycystin-1, including an autosomal dominant polycystic kidney disease (ADPKD)-associated mutation, significantly reduced PP1α-mediated dephosphorylation of polycystin-1. The results suggest that polycystin-1 forms a holoenzyme complex with PP1α via a conserved PP1-binding motif within the polycystin-1 C-tail, and that PKA-phosphorylated polycystin-1 serves as a substrate for the holoenzyme.
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影响因子：
10.5
作者：
Harris PC;Torres VE
通讯作者：
Torres VE
影响因子：
15.9
作者：
Chauvet, V;Tian, X;Caplan, MJ
通讯作者：
Caplan, MJ
影响因子：
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作者：
Hurley, Thomas D.;Yang, Jie;DePaoli-Roach, Anna A.
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3.3
作者：
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DOI：
10.1016/j.bbadis.2010.11.006
发表时间：
2011-10-01
影响因子：
6.2
作者：
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通讯作者：
Sandford, Richard N.