This table lists proteins that have been shown to interact with PP2A. These interactions have been detected in a variety of ways including yeast two-hybrid assays, direct binding, and functional assays.
|Adenomatous Polyposis Coli (APC)||Binds to R5 subunits; may target PP2A to APC complex involved in regulating b-catenin levels and Wnt signaling pathway; overexpression of R5 decreases β-catenin levels||1, 2|
|Adenovirus E4orf4 protein||Binds to AC-R2 complex; formation of complex required for E4orf4-mediated apoptosis||3, 4|
|Axin (Axin 1)||Binds to C subunit; may target PP2A to a complex of axin, APC, GSK3, and β-catenin; suggests involvement in Wnt signaling pathway||2, 5|
|Bcl-2||Bcl-2 interacts with PP2A; PP2A dephosphorylates Bcl-2; may regulate function of Bcl-2 in apoptosis; dephosphorylation of Bcl-2 is stimulated by ceramide||6, 7|
|β-adrenergic receptor||The β2-adrenergic receptor is a member of the G-protein coupled receptor family (GPCR). Association with PP2A is dependent on agonist stimulation, internalization, and acidification of endosomes. PP2A dephosphorylation of receptor is important for receptor resensitization and recycling to plasma membrane.||8|
|Biogenic amine transporters||Dopamine, norepinephrine, and serotonin transporters associate with PP2A. Transporter phosphorylation results in disruption of the PP2A association. The interaction may be involved in the regulation of the surface expression of transporters.||53|
|The Cα, but not the Cβ catalytic subunit of PP2A is required for stabilization of E-cadherin/β-catenin complexes at the plasma membrane||46|
|Calcium channel (L-type, Cav1.2)||PP2A binds to the pore-forming α1C subunit of this channel and reverses PKA-catalyzed serine phosphorylation. The interaction is selective for R5γ-containing PP2A complexes.||54|
|CaM kinase IV||Binds to AC-R2 complex; substrate for C subunit of PP2A. Disrupting the interaction with SV40 small-t antigen in transfected cells alters CaMKIV-dependent activation of CREB transcription factor.||9|
(p130 Crk-assoc substrate
|Cas is a Src substrate that has increased association with PP2A when Src is activated. PP2A dephosphorylates serine residues on Cas in vitro.||45|
|Casein kinase 2 (CK2)||CK2 binds to the AC dimer and stimulates phosphatase activity.||10|
|Caspase-3||Activates PP2A during apoptosis by proteolysis of the A subunit at a specific site. Enhanced dephosphorylation by PP2A may be important in apoptotic processes.||11|
|Cdc6||Cdc6 binds to R3/PR48 subunit; interacts with AC-PR48 complexes; may regulate DNA replication; overexpression of PR48 causes G1 arrest||12|
|Cdc25c||Cdc25c was shown to co-immunoprecipitate with PP2A from cells treated with a cross-linking reagent. Interaction appears to require R2 subunits and results in dephosphorylation of cdc25c. Interaction is enhanced by HIV-1 Vpr protein. Dephosphorylation and inactivation of cdc25c could be an important mechanism in Vpr-mediated G2 arrest.||13|
|This 450-kDa centrosome and golgi localized PKN-associated protein coimmunoprecipitates with PP2A in R3α-130 expressing cells. CG-NAP is involved in regulation of centrosome dynamics during the cell cycle.||59|
|CXCR2 is a member of the CXC chemokine receptor family. These are G-protein coupled receptors (GPCRs) involved in chemotaxis of lymphcytes and neutrophils. CXCR2 interacts with the core dimer (AC) of PP2A. The interaction is dependent on internalization of receptor following agonist stimulation.||14|
|Cyclin G1||Cyclin G1 binds to R5 subunits and the association is dependent on the induction of p53. Cyclin G1 plays a role in enhancing apoptosis.||15|
|Cyclin G2||The association of cyclin G2 with PP2A catalytic and R5 subunits correlates with its ability to inhibit cell cycle progression.||51|
|DNA polymerase α primase||PP2A is recovered with the hypophosphorylated form of DNA polymerase a-primase in G1. PP2A dephosphorylates DNA polymerase a-primase and restores its origin-dependent initiation activity in vito.||52|
|eRF1||Binds to AC dimer through C subunit; might target AC dimer to ribosomes||17|
|Estrogen receptorα||ERα co-immunoprecipitates with PP2A activity. The PP2A catalytic subunit binds to ERα and dephosphorylates Ser118.||61|
|HSF2||HSF2 interacts with the A subunit in two-hybrid assay and co-immunoprecipitations. May displace C subunit from PP2A holoenzymes.||18, 19|
|HIV Vpr protein||Binds to AC-R2 complex; mediates Vpr-induced G2 arrest; regulates nuclear Cdc25 dual-specificity phosphatase (NOTE: reference 21 has been retracted).||20, 21|
|HOX11||Binds to C subunit; inhibits phosphatase activity||22|
|HRX||Binds PP2A through I2PP2A; commonly mutated in acute leukemias||23|
|I1PP2A (PHAP1, mapmodulin)||Inhibitor of PP2A in vitro||24|
|I2PP2A (SET)||Inhibitor of PP2A in vitro|
|I-κB kinase (IKK) γ subunit||IKKγ interacts with PP2A as detected by co-immunoprecipitation and GST-fusion protein assays||60|
|JAK2||Transient association upon interleukin-11 stimulation of adipocytes||26|
|Kinase suppressor of Raf||KSR interacts with the R2α-containing isoform of the PP2A holoenzyme.|
|Mid-1||Mid-1 binds to the alpha 4 protein and forms a complex with the PP2A catalytic subunit. This interaction may regulate mid-1 bindng to microtubules and formation of the midline during the cell cycle.||60|
|Neurofilament proteins||A, R2, and C subunits associate with NF proteins; PP2A appears to dephosphorylate some sites in all three NF proteins (NF-L, NF-M, and NF-H); dephosphorylation by PP2A promotes assembly of NF-L||27, 28|
|NMDA receptor||PP2A forms a stable complex with NR3A subunit of the NMDA receptor. The association increases phosphatase activity and dephosphorylation of the NR1 subunit. Stimulation of the receptor leads to dissociation of PP2A and a reduction in phosphatase activity.||55|
|p107||p107 (an pRB-related protein) binds R3/PR59 subunit-containing holoenzyme; over-expression of R3/PR59 causes p107 dephosphorylation and G1 arrest.||29|
|p21-activated kinase (PAK1)||PAK1 is a PP2A substrate||30|
|p70 S6 kinase||p70 S6 kinase is a PP2A substrate||30, 31|
|PKCa||The PP2A catalytic subunit co-immunoprecipitates with PKCa. PKCa is dephosphorylated by PP2A. This association may be involved in the regulation of mast cell IL-6 production.||56|
|PKCδ||PKCd is a substrate for PP2A.||57|
|PKR (EIF2AK1, PRKR)||PKR binds to and phosphorylates the R5α regulatory subunit. This functional interaction may alter the activity of the translation initiation factor eIF4.||16|
|Polyomavirus middle tumor antigen||Binds to AC dimer; increases tyrosine phosphatase activity of PP2A||32, 33|
|Polyomavirus small tumor antigen||Similar to polyoma small t; binds to AC dimer; increases tyrosine phosphatase activity of PP2A||32, 33|
|Raf-1||Raf-1 can be dephosphorylated by PP2A||34|
|RelA||RelA interacts with the scaffold subunit of PP2A in vitro. The association may be transient since cross-linking is required to isolate the PP2A/RelA complex. RelA is dephosphorylated by PP2A in vitro.||47|
|Sex combs reduced (SCR)||SCR is a Drosophila homeobox transcription factor that interacts with the Drosophila homolog of the R5 subunit. SCR is highly homologous to human and mouse homeobox 5 and 6 proteins (HOX5 and HOX6).||35|
|SG2NA||Binds AC dimer, localized in nucleus, contains WD repeats, binds calmodulin, unknown function||36|
|Shc||PP2A associates with the PTB domain of Shc in the basal state and dissociates in response to insulin- and EGF-induced tyrosine phosphorylation. Expression of SV40 small-t antigen also causes dissociation of this complex.||48|
|Sp1||The Sp1 transcription factor interacts with the catalytic subunit in dividing T lymphocytes.||49|
|Src||PP2A binds to the SH2, SH3, and catalytic domains of Src. This interaction decreases Src tyrosine kinase activity.||58|
|STAT5||STAT5 associates with PP2A in an IL-3-dependent manner in the cytoplasm but not the nucleus.||50|
|Striatin||Binds to AC dimer, localized in post-synaptic densities of neuronal dendrites, contains WD repeats, binds calmodulin, unknown function||36|
|SV40 small tumor antigen||Binds to AC dimer; displaces R2 subunits; inhibits PP2A activity||32|
|Tap42/alpha 4 (IGBP1)||Interacts directly with the C subunit; also binds to PP4 and PP6; reduces the activity of the C subunit. Yeast homologue (Tap42) phosphorylated by Tor kinase which enhances association with the C subunit.||37-42|
|TAU||Binds to R2-containing trimers and is a good substrate for PP2A; TAU dephosphorylation promotes microtubule binding and stabiliztion||43|
|Tax||The human T-lymphotropic retrovirus type-I transactivator Tax interacts via a tripartite protein interaction that also involves IKKγ. The association of Tax with this complex inhibits PP2A activity and enhances the activity of IKK.||60|
|Vimentin||The AC-R2 complex associates with and dephosphorylates vimentin; association is mediated by R2; depletion of R2 by antisense RNA cause hyperphosphorylation of vimentin.||44|
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