Product Pathways - Translational Control
MetAP2 (D3I1H) Rabbit mAb #12547
|12547S||100 µl (10 western blots)||---||In Stock||---|
|12547||carrier free and custom formulation / quantity||email request|
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|W||1:1000||Human, Mouse, Rat, Monkey||Endogenous||63||Rabbit IgG|
Species cross-reactivity is determined by western blot.
Applications Key: W=Western Blotting
Species predicted to react based on 100% sequence homology: Hamster, Dog, Pig, Horse.
Specificity / Sensitivity
MetAP2 (D3I1H) Rabbit mAb recognizes endogenous levels of total MetAP2 protein. Based upon sequence alignment, this antibody is not predicted to cross-react with MetAP1.
Source / Purification
Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Gly390 of human MetAP2 protein.
Western blot analysis of extracts from various cell lines using MetAP2 (D3I1H) Rabbit mAb.
Eukaryotic initiation factor 2 (eIF2)-associated glycoprotein, p67/methionine aminopeptidase 2 (MetAP2) is one of the three known MetAPs responsible for the co-translational processing of the N-terminal initiator methionine from nascent proteins in cells. MetAP2 regulates the rates of global protein synthesis by controlling the levels of eIF2α phosphorylation (1). MetAP2 has also been shown to bind Erk1/2 to inhibit their activation and activity, thus connecting the protein synthesis machinery with the cell signaling pathway mediated by Erk1/2 MAP kinases (2-4). Although MetAP2 is characterized as having aminopeptidase activity that removes the N-terminal methionine from nascent peptides in vitro, mounting evidence suggests that MetAP2 has no methionine aminopeptidase activity. Rather, MetAP2 possesses auto-proteolytic activity that can be inhibited by several small molecule inhibitors including anti-angiogenic drugs, fumagillin and its derivatives (5). It has also been demonstrated that O-GlcNAcylation of MetAP2 plays a major role in its stability, eIF2α binding, and maintenance of eIF2α phosphorylation (6).
MetAP2 knockout mice show embryonic lethality, suggesting its role in embryonic development and survival at the initiation of gastrulation (7). It is likely that lowering the levels of MetAP2 in mammalian cells causes cell growth inhibition and leads to apoptosis due to the high levels of eIF2α phosphorylation that inhibits global protein synthesis (8). During pathological or various stress conditions, MetAP2 dissociates from eIF2 subunits possibly due to its deglycosylation-induced autoproteolytic cleavage. As a result, eIF2α becomes hyperphosphorylated and global protein synthesis is inhibited. eIF2 complex-dissociated MetAP2 also displays a higher affinity toward Erk1/2, which results in the blockade of Erk1/2 activity. Thus, MetAP2 mediates cooperation between cell signaling and protein synthesis machinery to regulate cell growth and proliferation during physiological and pathological conditions (9). Research studies have shown higher expression of MetAP2 in human cancers, supporting the contention that MetAP2 plays a role in oncogenesis. For example, investigators have reported high MetAP2 expression in follicular lymphomas, large B-cell lymphomas, and Burkitt's lymphomas (10). Elevated expression of MetAP2 has also been reported in human colorectal adenocarcinomas (11).
- Datta, B. (2000) Biochimie 82, 95-107.
- Datta, B. et al. (2004) Arch Biochem Biophys 427, 68-78.
- Datta, B. et al. (2004) Biochemistry 43, 14821-31.
- Datta, B. et al. (2005) Exp Cell Res 303, 174-82.
- Bradshaw, R.A. and Yi, E. (2002) Essays Biochem 38, 65-78.
- Datta, B. et al. (1999) Exp Cell Res 250, 223-30.
- Yeh, J.R. et al. (2006) Proc Natl Acad Sci U S A 103, 10379-84.
- Datta, B. and Datta, R. (1999) Exp Cell Res 246, 376-83.
- Ghosh, A. et al. (2006) Exp Cell Res 312, 3184-203.
- Kanno, T. et al. (2002) Lab Invest 82, 893-901.
- Selvakumar, P. et al. (2004) Clin Cancer Res 10, 2771-5.
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For Research Use Only. Not For Use In Diagnostic Procedures.
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