Specific regulation of protein phosphatase 2A PR72/B′′ subunits by calpain

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• 作者：Veerle Janssens ; Rita Derua ; Karen Zwaenepoel ; EtienneWaelkens ; Jozef Goris
• 关键词：Protein phosphatase 2A ; Calpain ; Ca²⁺-signaling ; Protease ; EF-hand ; Phosphatase assay ; Polycations ; PEST-domain ; Apoptosis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：4 September 2009
• 年：2009
• 卷：386
• 期：4
• 页码：676-681
• 全文大小：533 K

文摘

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 Ca²⁺-binding EF-hands in the PR72/B′′ class of regulatory PP2A subunits. Now we report partial degradation of PR72/B”α2 and PR130/B”α1 into a 45–48 kDa proteolysis-resistant fragment (‘PR45’) by the Ca²⁺-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.