Specific regulation of protein phosphatase 2A PR72/B" subunits by calpain
Specific regulation of protein phosphatase 2A PR72/B" subunits by calpain
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DOI：
10.1016/j.bbrc.2009.06.096
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发表时间：
2009-09-04
影响因子：
3.1
通讯作者：
Goris, Jozef
中科院分区：
文献类型：
--
作者：
Janssens, Veerle;Derua, Rita;Goris, Jozef
蛋白磷酸酶2A（PP 2A）是一个多聚体丝氨酸/苏氨酸磷酸酶家族，在信号转导中具有多效性作用。我们先前描述了两个Ca（2+）-结合EF-手在PR 72/B“类调节PP 2A亚基中的功能分析。现在我们报道了PR 72/B“α 2和PR 130/B”α 1被Ca（2+）依赖性蛋白酶m-calpain部分降解为45-48 kDa的抗蛋白水解片段（“PR 45”）。这种有限的蛋白水解依赖于EF-手完整性，独立于两个PEST-结构域，并且高度特异性，因为PP 2A（C）、PR 65/A和PR 55/B和PR 61/B'亚基家族的代表是钙蛋白酶抗性的。PR 45也在星形孢菌素诱导的凋亡MCF 7细胞中以钙蛋白酶依赖的方式产生。钙蛋白酶治疗减弱了PR 72-核心酶的相互作用，激活了基础PP 2A（T72）磷酸酶活性，并显着增加了其敏感性和激活聚阳离子。这种独特的性质可以利用在一个特定的生化测定这些全酶。我们建议在体内的局部钙蛋白酶的行动可能构成一种新的监管机制，这些全酶。(C)2009 Elsevier Inc. All rights reserved.
Protein phosphatase 2A (PP2A) represents a family of multimeric serine/threonine phosphatases with pleiotropic roles in signal transduction. We previously described the functional analysis of two Ca(2+)-binding EF-hands in the PR72/B '' class of regulatory PP2A subunits. Now we report partial degradation of PR72/B ''alpha 2 and PR130/B ''alpha 1 into a 45-48 kDa proteolysis-resistant fragment ('PR45') by the Ca(2+)-dependent protease m-calpain. This limited proteolysis is dependent on EF-hand integrity, independent of two PEST-domains, and highly specific as PP2A(C), PR65/A and representatives of PR55/B and PR61/B' subunit families are calpain-resistant. PR45 was also generated in staurosporine-induced apoptotic MCF7 cells in a calpain-dependent way. Calpain treatment weakens the PR72-core enzyme interaction, activates basal PP2A(T72) phosphatase activity and dramatically increases its sensitivity for and activation by polycations. This unique property can be exploited in a specific biochemical assay for these holoenzymes. We propose local calpain action in vivo may constitute a novel regulatory mechanism of these holoenzymes. (C) 2009 Elsevier Inc. All rights reserved.