Rabbit anti-Mouse MEK1/2 (Ser218,222) Polyclonal Antibody | anti-MAP2K1/2 antibody

Anti-Phospho-Ser218,222 MEK 1/2

Cat. Num. AAA502074

• Gene Names: MAP2K1; CFC3; MEK1; MKK1; MAPKK1; PRKMK1
• Reactivity: Mouse
• Applications: Western Blot
• Purity: Affinity Purified (Prepared from rabbit serum by affinity purification via sequential chromatography on phospho- and dephosphopeptide affinity columns.)
• Synonyms: MEK1/2 (Ser218; 222); Polyclonal Antibody; Anti-Phospho-Ser218; 222 MEK 1/2; anti-MAP2K1/2 antibody

• Host: Rabbit
• Reactivity: Mouse
• Clonality: Polyclonal
• Specificity: Specific for the ~45k MEK 1/2 protein phosphorylated at Ser218/222 in Western blots. Immunolabeling is blocked by the phosphopeptide used as the antigen but not by the corresponding dephosphopeptide.
• Purity/Purification: Affinity Purified (Prepared from rabbit serum by affinity purification via sequential chromatography on phospho- and dephosphopeptide affinity columns.)
• Form/Format: 100 ul in 10 mM HEPES (pH 7.5), 150 mM NaCl, 100 ug per ml BSA and 50% glycerol. Adequate amount of material to conduct 10-mini Western Blots.
• Sequence Length: 393

• Applicable Applications for anti-MAP2K1/2 antibody: Western Blot (WB)
• Application Notes: Quality Control: Western blots performed on each lot.; WB: 1:1000
• Antigen: Phosphopeptide corresponding to amino acid residues surrounding the phospho-Ser218,222 of human MEK 1/2. Note: The phosphosites in human MEK 1/2 are Ser218 and Ser222; the phosphosites in mouse MEK 1/2 are Ser217 and Ser221.
• Immunogen Information: Synthetic phospho-peptide corresponding to amino acid residues surrounding Ser218/222 conjugated to KLH
• Immunogen Species: Human
• Reactivity Assumed Based on 100% Sequence Homology: Bovine, canine, chicken, human, non-human primates, rat, Xenopus and zebra fish
• Species Reactivity Note: The antibody has been directly tested for reactivity in Western blots with mouse tissue. It is anticipated that the antibody will react with bovine, canine, chicken, human, non-human primates, rat, Xenopus and zebra fish based on the fact that these species have 100% homology in the amino acid sequence used as antigen for this antibody.
• Biological Significance: MEK 1 (MAP Kinase Kinase, also known as MKK) is an integral component of the MAP kinase cascade that regulates cell growth and differentiation (Ahn, 1993; Chong et al., 2003). This pathway also plays a key role in synaptic plasticity in the brain (Adams and Sweatt, 2002). Activated MEK 1 acts as a dual specificity kinase phosphorylating both a threonine and a tyrosine residue on MAP kinase (Kyriakis et al., 1991; Seger et al., 1991; Crews et al., 1992).
• Preparation and Storage: For long term storage -20 degree C is recommended. Stable at -20 degree C for at least 1 year.

Testing Data

Related Product Information for anti-MAP2K1/2 antibody

Affinity purified rabbit polyclonal antibody

References

• Adams JP, Sweatt JD (2002) Molecular psychology: Roles for the ERK MAP kinase cascade in memory. Annu Rev Pharmacol Toxicol 42:135-163.
• Ahn NG (1993) The MAP kinase cascade. Discovery of a new signal transduction pathway. Mol Cell Biochem 127-128:201-209. Chong H, Vikis HG, Guan KL (2003) Mechanisms of regulating the Raf kinase family. Cellular Signalling 15:463-469.
• Crews CM, Alessandrini A, Erikson RL (1992) The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. Science 258:478-480.
• Kyriakis JM, Brautigan DL, Ingebritsen TS, Avruch J (1991) pp54 Microtubule-associated protein-2 kinase requires both tyrosine and serine/threonine phosphorylation for activity. J Biol Chem 266:10043-10046.
• Seger R, Ahn NG, Boulton TG, Yancopoulos GD, Panayotatos N, Radziejewska E, Ericsson L, Bratlien RL, Cobb MH, Krebs EG (1991) Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophos-phorylation on both tyrosine and threonine residues: Implications for their mechanism of activation. Proc Natl Acad Sci USA 88:6142-6146.

NCBI and Uniprot Product Information

• NCBI GI #: 5579478
• NCBI GeneID: 5604
• NCBI Accession #: NP_002746.1
• NCBI GenBank Nucleotide #: NM_002755.3
• UniProt Accession #: Q02750
• Molecular Weight: 45
• NCBI Official Full Name: dual specificity mitogen-activated protein kinase kinase 1
• NCBI Official Synonym Full Names: mitogen-activated protein kinase kinase 1
• NCBI Official Symbol: MAP2K1
• NCBI Official Synonym Symbols: CFC3; MEK1; MKK1; MAPKK1; PRKMK1
• NCBI Protein Information: dual specificity mitogen-activated protein kinase kinase 1; MEK 1; MAPKK 1; MAPK/ERK kinase 1; ERK activator kinase 1; protein kinase, mitogen-activated, kinase 1 (MAP kinase kinase 1)
• UniProt Protein Name: Dual specificity mitogen-activated protein kinase kinase 1
• UniProt Gene Name: MAP2K1
• UniProt Synonym Gene Names: MEK1; PRKMK1; MAP kinase kinase 1; MAPKK 1; MKK1; MEK 1
• UniProt Entry Name: MP2K1_HUMAN

NCBI Description

The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

Uniprot Description

Function: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. Ref.6 Ref.9

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation: Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222. MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A

By similarity. Many inhibitors have been identified including pyrrole derivatives, TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766.

Subunit structure: Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14

By similarity. Forms a heterodimer with MAP2K2/MEK2

By similarity. Forms heterodimers with KSR2 which further dimerize to form tetramers

By similarity. Interacts with ARBB2, LAMTOR3, MAPK1/ERK2, MORG1 and RAF1

By similarity. Interacts with PPARG and with isoform 1 of VRK2. Interacts with Yersinia yopJ. Interacts with SGK1. Interacts with BIRC6/bruce.

Subcellular location: Cytoplasm › cytoskeleton › microtubule organizing center › centrosome. Cytoplasm › cytoskeleton › microtubule organizing center › spindle pole body. Cytoplasm. Nucleus. Note: Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis. Ref.6 Ref.9

Tissue specificity: Widely expressed, with extremely low levels in brain. Ref.1

Domain: The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1

By similarity.

Post-translational modification: Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (RAF or MEKK1) positively regulates kinase activity. Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK. MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK. Ref.3 Ref.7Acetylation by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. Ref.8

Involvement in disease: Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.29 Ref.30

Sequence similarities: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.Contains 1 protein kinase domain.