PME-1 Antibody [L6L14] | Primary Antibodies

Application: Reactivity: Human, Mouse, Rat

Usage Information

Dilution
WB1:100-1:500 IP1:100-1:200 IHC1:50-1:500 IF1:50-1:500

Application
WB, IP, IF, FCM, ELISA

Reactivity
Human, Mouse, Rat

Source
Mouse Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
44 kDa

Datasheet & SDS

Biological Description

Specificity
PME-1 Antibody [L6L14] detects endogenous levels of total PME-1 protein.

Clone
L6L14

Synonym(s)
PPME1, Protein phosphatase methylesterase 1, EC:3.1.1.89, PME-1, PME1, PP2593, PRO0750

Background
Protein phosphatase methylesterase-1 (PME-1, also known as PP2A methylesterase 1) is a conserved serine hydrolase that regulates protein phosphatase 2A (PP2A), a central Ser/Thr phosphatase complex controlling cell growth, survival, and stress signaling, by reversing C-terminal methylation of the PP2A catalytic subunit and directly inhibiting the phosphatase active site. PME-1 has an α/β-hydrolase fold with a catalytic Ser-Asp-His triad typical of serine hydrolases, and N‑terminal low-complexity regions that contain short linear motifs used for docking to PP2A holoenzymes, including motifs that mimic PP2A substrates and engage specific regulatory B subunits. PME-1 demethylates PP2A by hydrolyzing the ester bond at the C-terminal leucine of the catalytic subunit, which removes the methyl group required for efficient association with a subset of regulatory B subunits and alters the composition and activity profile of PP2A holoenzymes, thereby shifting signaling output across pathways such as MAPK/ERK and AKT. PME-1 also binds directly to assembled PP2A core and B56-containing holoenzymes, occupies the catalytic groove, and blocks access of phospho-substrates, so that a single PME-1 molecule can both demethylate the catalytic tail and inhibit PP2A catalytic activity toward bound substrates in the same complex. PME-1 disordered N-terminal regions tether to multiple remote sites on the B56 regulatory subunit, including a substrate-mimicking motif that inserts into the canonical substrate-binding groove, while large conformational shifts in both PME-1 and the holoenzyme bring the PME-1 catalytic core into position to access the methylated PP2A tail and enforce active-site inhibition, defining a multipartite interaction mechanism that couples holoenzyme recognition to methylesterase activation. These binding modes enable PME-1 to demethylate different families of PP2A holoenzymes and to broadly suppress PP2A holoenzyme functions, with B56 interface mutations selectively blocking PME-1 activity toward PP2A-B56 complexes and altering methylation of a defined fraction of cellular PP2A, including pools involved in p53 signaling. In cancer models such as glioma and endometrial carcinoma, PME-1 overexpression reduces PP2A tumor suppressor activity, sustains ERK and AKT pathway signaling, and supports malignant phenotypes including increased proliferation, invasion, and resistance to kinase inhibitors, and PME-1 levels are elevated in clinical tumor specimens where they correlate with progression.

Background

Protein phosphatase methylesterase-1 (PME-1, also known as PP2A methylesterase 1) is a conserved serine hydrolase that regulates protein phosphatase 2A (PP2A), a central Ser/Thr phosphatase complex controlling cell growth, survival, and stress signaling, by reversing C-terminal methylation of the PP2A catalytic subunit and directly inhibiting the phosphatase active site. PME-1 has an α/β-hydrolase fold with a catalytic Ser-Asp-His triad typical of serine hydrolases, and N‑terminal low-complexity regions that contain short linear motifs used for docking to PP2A holoenzymes, including motifs that mimic PP2A substrates and engage specific regulatory B subunits. PME-1 demethylates PP2A by hydrolyzing the ester bond at the C-terminal leucine of the catalytic subunit, which removes the methyl group required for efficient association with a subset of regulatory B subunits and alters the composition and activity profile of PP2A holoenzymes, thereby shifting signaling output across pathways such as MAPK/ERK and AKT. PME-1 also binds directly to assembled PP2A core and B56-containing holoenzymes, occupies the catalytic groove, and blocks access of phospho-substrates, so that a single PME-1 molecule can both demethylate the catalytic tail and inhibit PP2A catalytic activity toward bound substrates in the same complex. PME-1 disordered N-terminal regions tether to multiple remote sites on the B56 regulatory subunit, including a substrate-mimicking motif that inserts into the canonical substrate-binding groove, while large conformational shifts in both PME-1 and the holoenzyme bring the PME-1 catalytic core into position to access the methylated PP2A tail and enforce active-site inhibition, defining a multipartite interaction mechanism that couples holoenzyme recognition to methylesterase activation. These binding modes enable PME-1 to demethylate different families of PP2A holoenzymes and to broadly suppress PP2A holoenzyme functions, with B56 interface mutations selectively blocking PME-1 activity toward PP2A-B56 complexes and altering methylation of a defined fraction of cellular PP2A, including pools involved in p53 signaling. In cancer models such as glioma and endometrial carcinoma, PME-1 overexpression reduces PP2A tumor suppressor activity, sustains ERK and AKT pathway signaling, and supports malignant phenotypes including increased proliferation, invasion, and resistance to kinase inhibitors, and PME-1 levels are elevated in clinical tumor specimens where they correlate with progression.

References
https://pubmed.ncbi.nlm.nih.gov/10318862/ https://pubmed.ncbi.nlm.nih.gov/35924897/

Reference Table for Selecting PVDF Membrane Pore Size Specifications

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%