complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A, regulatory B subunit, B56"))

Components

• p(HGNC:PPP2CA)
• p(HGNC:PPP2R1A)
• p(INTERPRO:"Protein phosphatase 2A, regulatory B subunit, B56")

To gain full activity towards specific substrates, the PP2A core enzyme interacts with a variable regulatory subunit to form a heterotrimeric holoenzyme. The variable regulatory subunits consist of four families: B (also known as B55 or PR55), B′ (B56 or PR61), B′′ (PR48/PR72/PR130), and B′′′ (PR93/PR110), with at least 16 members in these families PubMed:19277525

Except the B′′′ subunits, direct interactions between the PP2A core enzyme and the regulatory subunits have been demonstrated PubMed:19277525

By contrast, several recent studies using purified, recombinant proteins showed that the methylation status of the catalytic subunit did not play a decisive role for the in vitro assembly of PP2A holoenzymes involving the B and B′ subunit PubMed:19277525

Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the catalytic subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits PubMed:19277525

Neither mutation of the carboxy-terminal Leu residue nor removal of the carboxy-terminal 14 amino acids of the catalytic subunit prevented formation of heterotrimeric holoenzymes involving the B or B′ subunits PubMed:19277525

For example, the PP2A holoenzyme involving the B′ family plays an essential role in cell-cycle progression, through direct interaction with the protein Shugoshin PubMed:19277525

The specificity in this in vitro system is quite robust, as evidenced by the observation that the PP2A core enzyme exhibited a lower activity to dephosphorylate the Tau protein than the PP2A holoenzyme involving the B subunit, but a higher activity than the holoenzyme involving the B′ subunit PubMed:19277525