Abstract
BackgroundProtein phosphatase 2A (PP2A) is a serine/threonine-specific phosphatase displaying vital functions in growth and development through its role in various signalling pathways. PP2A holoenzymes comprise a core dimer composed of a catalytic C and a structural A subunit, which can associate with a variable B-type subunit. The importance of the B-type subunits for PP2A regulation cannot be overestimated as they determine holoenzyme localisation, activity and substrate specificity. Three B-type subunit families have been identified: PR55/B, PR61/B' and PR72/B", of which the latter is currently the least characterised.ResultsWe deduced the sequences and genomic organisation of the different murine PR72/B" isoforms: three genes encode nine isoforms, five of which are abundantly expressed and give rise to genuine PP2A subunits. Thereby, one novel subunit was identified. Using Northern blotting, we examined the tissue-specific and developmental expression of these subunits. All subunits are highly expressed in heart, suggesting an important cardiac function. Immunohistochemical analysis revealed a striated expression pattern of PR72 and PR130 in heart and skeletal muscle, but not in bladder smooth muscle. The subcellular localisation and cell cycle regulatory ability of several PR72/B" isoforms were determined, demonstrating differences as well as similarities.ConclusionIn contrast to PR55/B and PR61/B', the PR72/B" family seems evolutionary more divergent, as only two of the murine genes have a human orthologue. We have integrated these results in a more consistent nomenclature of both human and murine PR72/B" genes and their transcripts/proteins. Our results provide a platform for the future generation of PR72/B" knockout mice.
Highlights
Protein phosphatase 2A (PP2A) is a serine/threonine-specific phosphatase displaying vital functions in growth and development through its role in various signalling pathways
The murine B" family isoforms In mammals, four genes of the B" regulatory subunit family of PP2A have been described, giving rise to six isoforms: PR72 [6], PR130 [6], PR70 [7], PPP2R3L product [8], G5PR [9] and mPR59, an isoform sofar only found in mice [10]
An important difference with the PR55/B and PR61/ B' families is the poorer relationship between human and murine genes, which might indicate that the B" family is evolutionary more divergent
Summary
Protein phosphatase 2A (PP2A) is a serine/threonine-specific phosphatase displaying vital functions in growth and development through its role in various signalling pathways. PP2A holoenzymes comprise a core dimer composed of a catalytic C and a structural A subunit, which can associate with a variable B-type subunit. The importance of the B-type subunits for PP2A regulation cannot be overestimated as they determine holoenzyme localisation, activity and substrate specificity. The core of PP2A consists of a structural PR65/A subunit and a catalytic C subunit, both existing in two isoforms, α and β. To this PP2A dimer (PP2AD), a third regulatory B-type subunit can bind. At present approximately 20 regulatory B-type subunits have been described Based on their primary structure, they can be divided into three families: PR55/B, PR61/B' ( called B56) and PR72/B" [1]. Phosphorylation and methylation of the catalytic C subunit play an important role in the assembly of specific trimeric holoenzymes [4,5]
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