Product Pathways - Phosphatases

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PP2C-α (D18C10) XP^® Rabbit mAb #3549

Applications	Reactivity	Sensitivity	MW (kDa)	Isotype
W IP IHC-P IF-IC F	H Mk	Endogenous	43	Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation  IHC-P=Immunohistochemistry (Paraffin)  IF-IC=Immunofluorescence (Immunocytochemistry)  F=Flow Cytometry
Reactivity Key:  H=Human  Mk=Monkey
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

3549:

Flow, IHC / Paraffin, Immunofluorescence, Immunoprecipitation, Western Blotting

Specificity / Sensitivity

PP2C-α (D18C10) XP^® Rabbit mAb detects endogenous levels of total PP2C-α protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ser375 of human PP2C-α.

Background

The α isoform of protein phosphatase 2C (PP2C-α) is the catalytic subunit of a widely expressed serine/threonine phosphatase involved in regulation of the cell stress response (1,2). Also known as magnesium-dependent protein phosphatase (PPM1A), this monomeric phosphatase is a member of a conserved group of proteins that acts on many different substrates in numerous pathways. PP2C-α inhibits p38 MAPK and SAPK/JNK pathways activated in response to cell stress as seen in both in vivo and in vitro studies. Specifically, PP2C-α removes phosphates from MKK3 and MKK7, reducing activity of both proteins and inhibiting activation of the downstream kinases JNK and p38 MAPK, respectively (3). Another PP2C-α substrate is IKKβ, the critical regulator of NF-κB signaling. Dephosphorylation of IKKβ at Ser177/181 by PPM1A and PPM1B results in inactivation of IKKβ and inhibition of NF-κB signaling (4). PP2C-α is one of the phosphatases responsible for removing phosphate residues from cyclin dependent protein kinases. In a study using HeLa cell extracts, PP2C-α dephospohrylates CDK2 and CDK6, with a preference toward interacting with CDK2 phosphorylated at Thr160, a residue found in the activating T-loop of the kinase. Removal of phosphates from this site is thought to inactivate cyclin-associated kinases (5). PP2C-α induces cell cycle arrest and apoptosis, likely through activation of p53 though other pathways may also contribute to PP2C-α mediated cell death (6). Additional PP2C-α substrates include the Wnt signaling pathway protein axin (7) and CFTR, a chloride channel protein implicated in cystic fibrosis (8).

1. Marley, A.E. et al. (1998) FEBS Lett 431, 121-4.
2. Stern, A. et al. (2007) J Mol Evol 64, 61-70.
3. Takekawa, M. et al. (1998) EMBO J 17, 4744-52.
4. Sun, W. et al. (2009) Cell Signal 21, 95-102.
5. Cheng, A. et al. (2000) J Biol Chem 275, 34744-9.
6. Ofek, P. et al. (2003) J Biol Chem 278, 14299-305.
7. Strovel, E.T. et al. (2000) J Biol Chem 275, 2399-403.
8. Travis, S.M. et al. (1997) Proc Natl Acad Sci USA 94, 11055-60.

Application References

• Chida, T. et al. (2013) Biochem J 449, 741-9. Applications: Western Blotting

Have you published research involving the use of our products? If so we'd love to hear about it. Please let us know!

Companion Products

• 7071 Phototope^®-HRP Western Blot Detection System, Anti-rabbit IgG, HRP-linked Antibody
• 7074 Anti-rabbit IgG, HRP-linked Antibody
• 7720 Prestained Protein Marker, Broad Range (Premixed Format)
• 7727 Biotinylated Protein Ladder Detection Pack
• 7003 20X LumiGLO^® Reagent and 20X Peroxide
• 8112 SignalStain^® Antibody Diluent

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For Research Use Only. Not For Use In Diagnostic Procedures.