phosphatase-2A (ceramide-activated protein phosphatase)

Function

• exhibits broad specificity
• PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, & MAP-2 kinase

can dephosphorylate SV40 large T antigen & p53

dephosphorylates SV40 large T antigen, preferentially on Ser-120, 123, 677, & perhaps 679

C subunit was most active, followed by the AC form, which was more active than the ABC form, & activity of all 3 forms was strongly stimulated by Mn+2, & to a lesser extent by Mg+2

dephosphorylation by the AC form, but not C or ABC form is inhibited by small T antigen

PP2A consists of a common heterodimeric core enzyme

composed of a 36 kD catalytic subunit (subunit C) & a 65 kD constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits.

proteins that associate with the core dimer include 3 families of regulatory subunits B (the R2/B/PR55/B55, R 3/B''/PR72/PR130/PR59 & R5/B'/B56 families), the 48 kD variable regulatory subunit, viral proteins, & cell signaling molecules

the PP2A-B subunit appears to suppress the activity of PP2A

ceramide activates heterotrimeric PP2A, but not PP2A- catalytic monomer or PP2A-cat/PP2A-A hetero-dimer, thus appears to act via removing inhibition by the PP2A-B subunit

PP2A is conformation-specific & effectively dephosphorylates the trans pSer/Thr-Pro isomer only.

Compartment

associates with microtubules

Expression

abundant in brain[4]

Notes

inhibited by calyculin A & okadaic acid

More general terms

• serine/threonine phosphatase
• nuclear protein
• multisubunit protein