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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. [3] Compartment: associates with microtubules [4] Expression: abundant in brain[4] Notes: inhibited by calyculin A & okadaic acid [4]

Interactions

molecular events

General

multisubunit protein nuclear protein serine/threonine phosphatase

Properties

COMPARTMENT: cell nucleus cytoplasm MOTIF: active site Ser-phosphate (2) STATE: active state SUBUNITS: phosphatase 2A catalytic subunit MOTIF: active site STATE: active state phosphatase 2 regulatory subunit A MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl consensus repeat (15) phosphatase-2A B subunit MOTIF: binding site FOR-BINDING-OF: ceramide MISC-INFO: INHIBITOR = OKADAIC_ACID Ki [Al+3] 40-60 MM LIGAND = HISTONE_H1

References

  1. Armstrong DL Calcium channel regulation by calcineurin, a Ca+2-activated phosphatase in mammalian brain TINS 12(3):117 1989 PMID: 2469218
  2. Hannun YA, Obeid LM. Ceramide: an intracellular signal for apoptosis. Trends Biochem Sci. 1995 Feb;20(2):73-7. Review. PMID: 7701566
  3. Zhou XZ, Kops O, Werner A, Lu PJ, Shen M, Stoller G, Kullertz G, Stark M, Fischer G, Lu KP. Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins. Mol Cell. 2000 Oct;6(4):873-83. PMID: 11090625
  4. Kosik KS, Shimura H. Phosphorylated tau and the neurodegenerative foldopathies. Biochim Biophys Acta. 2005 Jan 3;1739(2-3):298-310. Epub 2004 Nov 26. Review. PMID: 15615647

Component-of

molecular complex

Components

phosphatase-2A B subunit protein phosphatase 2 regulatory subunit A (phosphatase-2A A subunit) protein phosphatase-2A catalytic subunit; phosphatase 2 catalytic subunit