catalog number :
MBS502072
products full name :
Anti-Phospho-Thr292 MEK 1
products short name :
MEK1 (Thr292)
other names :
dual specificity mitogen-activated protein kinase kinase 1; Dual specificity mitogen-activated protein kinase kinase 1; 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); mitogen-activated protein kinase kinase 1; ERK activator kinase 1; MAPK/ERK kinase 1
products gene name :
MAP2K1
other gene names :
MAP2K1; MAP2K1; CFC3; MEK1; MKK1; MAPKK1; PRKMK1; MEK1; PRKMK1; MAP kinase kinase 1; MAPKK 1; MKK1; MEK 1
uniprot entry name :
MP2K1_HUMAN
specificity :
Specific for the ~45k MEK 1 protein phosphorylated at Thr292 in Western blots.
purity :
Affinity Purified (Prepared from rabbit serum by affinity purification via sequential chromatography on phospho- and dephosphopeptide affinity columns.)
form :
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.
storage stability :
For long term storage -20 degree C is recommended. Stable at -20 degree C for at least 1 year.
tested application :
Western Blot (WB)
app notes :
Quality Control: Western blots performed on each lot. WB: 1:1000
other info1 :
Antigen: Phosphopeptide corresponding to amino acid residues surrounding the phospho-Thr292 of human MEK 1. Immunogen Information: Synthetic phospho-peptide corresponding to amino acid residues surrounding Thr292 conjugated to KLH. Immunogen Species: Human
other info2 :
Reactivity Assumed Based on 100% Sequence Homology: Bovine, canine, human, mouse, non-human primates and rat. Species Reactivity Note: The antibody has been directly tested for reactivity in Western blots with recombinant MEK1. It is anticipated that the antibody will react with bovine, canine, human, mouse, non-human primates and rat based on the fact that these species have 100% homology with the amino acid sequence used as antigen. 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). Conversely, there also appears to be a feedback phosphorylation of MEK 1 by MAP kinase. The sites on MEK 1 that are phosphorylated by MAP kinase are Thr292 and Thr386 (Mansour et al., 1994).
products description :
Affinity purified rabbit polyclonal antibody
products 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. Mansour SJ, Resing KA, Candi JM, Hermann AS, Gloor JW, Herskind KR, Wartmann M, Davis RJ, Ahn NG (1994) Mitogen-activated protein (MAP) kinase phosphorylation of MAP kinase kinase: Determination of phosphorylation sites by mass spectrometry and site-directed mutagenesis. J Biochem (Tokyo) 116:304-314. 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 acc num :
NP_002746.1
ncbi gb acc num :
NM_002755.3
ncbi pathways :
AGE/RAGE Pathway (698754); ARMS-mediated Activation Pathway (106466); Activated TLR4 Signalling Pathway (106400); Acute Myeloid Leukemia Pathway (83117); Acute Myeloid Leukemia Pathway (529); Alcoholism Pathway (585563); Alcoholism Pathway (587116); Axon Guidance Pathway (105688); B Cell Receptor Signaling Pathway (198909); B Cell Receptor Signaling Pathway (83081)
ncbi summary :
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 summary :
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.