The C-terminus of NIPP1 (nuclear inhibitor of protein phosphatase-1) contains a novel binding site for protein phosphatase-1 that is controlled by tyrosine phosphorylation and RNA binding
The C-terminus of NIPP1 (nuclear inhibitor of protein phosphatase-1) contains a novel binding site for protein phosphatase-1 that is controlled by tyrosine phosphorylation and RNA binding
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DOI：
10.1042/0264-6021:3520651
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发表时间：
2000-12-15
影响因子：
4.1
通讯作者：
Bollen, M
中科院分区：
文献类型：
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作者：
Beullens, M;Vulsteke, V;Bollen, M
蛋白磷酸酶-1核抑制剂（NIPP1； 351个残基）是一种核rna结合蛋白，其中心结构域也含有与蛋白磷酸酶-1催化亚基相互作用的两个连续位点（PP1(c)）。我们在这里表明，这些磷酸酶相互作用位点的突变并没有完全消除NIPP1结合和抑制PP1的能力(c)。这可能是由于在c端区域（残基311-351）有一个额外的抑制性磷酸酶结合位点，其抑制核心对应于残基331-337。在中心和c端结构域的所有三个PP1(c)结合位点发生突变后，NIPP1不再与PP1(c)相互作用。值得注意的是，虽然两个NIPP1结构域都独立抑制PP1(c)的磷酸化酶磷酸酶活性，但任何一个结构域的突变都完全取消了NIPP1抑制髓鞘碱性蛋白去磷酸化的能力。NIPP1 c -末端的抑制效力通过tyr335的磷酸化和RNA的添加而降低。Tyr-335可以被酪氨酸激酶Lyn磷酸化，但只有在RNA存在的情况下。总之，NIPP1包含两个磷酸酶结合结构域，它们协同作用，但独立控制。我们的数据与PP1(c)与其调控亚基相互作用的共享位点模型一致。
Nuclear inhibitor of protein phosphatase-1 (NIPP1; 351 residues) is a nuclear RNA-binding protein that also contains in its central domain two contiguous sites of interaction with the catalytic subunit of protein phosphatase-1 (PP1(c)). We show here that mutation of these phosphatase-interaction sites did not completely abolish the ability of NIPP1 to bind and inhibit PP1(c). This could be accounted for by an additional inhibitory phosphatase-binding site in the C-terminal region (residues 311-351), with an inhibitory core corresponding to residues 331-337. Following mutation of all three PP1(c)-binding sites in the central and C-terminal domains, NIPP1 no longer interacted with PP1(c). Remarkably, while both NIPP1 domains inhibited the phosphorylase phosphatase activity of PP1(c) independently, mutation of either domain completely abolished the ability of NIPP1 to inhibit the dephosphorylation of myelin basic protein. The inhibitory potency of the C-terminal site of NIPP1 was decreased by phosphorylation of Tyr-335 and by the addition of RNA. Tyr-335 could be phosphorylated by tyrosine kinase Lyn, but only in the presence of RNA. In conclusion, NIPP1 contains two phosphatase-binding domains that function co-operatively but which are controlled independently. Our data are in agreement with a shared-site model for the interaction of PP1(c) with its regulatory subunits.