SAPK/Erk kinase (SEK1), also known as MKK4 or Jun kinase kinase (JNKK), activates the MAP kinase homologues SAPK and JNK in response to various cellular stresses and inflamatory cytokines (1-3). Activation of SEK1 occurs through MEKK phosphorylation of serine and threonine residues at positions 257 and 261, respectively. Like MEK, SEK is a dual-specificity protein kinase that phosphorylates SAPK/JNK at a conserved T*PY* site in its activation loop (4). Phosphorylation by Akt at Ser80 inhibits SEK1 and suppresses stress-activated signal transduction (5).Davis, R.J. (1994) Trends Biochem. Sci. 19, 470-473. Sanchez, I. et al. (1994) Nature 372, 794-798. Yan, M. et al. (1994) Nature 372, 798-800. Kyriakis, J.M. et al. (1994) Nature 369, 156-160. Park, H. et al. (2002) J. Biol. Chem. 277, 2573-2578.
Host
Rabbit
Immunogen
Peptide sequence around aa.352~356(E-S-K-R-P)derived from Human MAP2K4.
Raised In
Rabbit
Reactivity
Human, Mouse, Rat
Regulatory
RUO
Relevance
SAPK/Erk kinase (SEK1), also known as MKK4 or Jun kinase kinase (JNKK), activates the MAP kinase homologues SAPK and JNK in response to various cellular stresses and inflamatory cytokines (1-3). Activation of SEK1 occurs through MEKK phosphorylation of serine and threonine residues at positions 257 and 261, respectively. Like MEK, SEK is a dual-specificity protein kinase that phosphorylates SAPK/JNK at a conserved T*PY* site in its activation loop (4). Phosphorylation by Akt at Ser80 inhibits SEK1 and suppresses stress-activated signal transduction (5).
Davis, R.J. (1994) Trends Biochem. Sci. 19, 470-473. Sanchez, I. et al. (1994) Nature 372, 794-798. Yan, M. et al. (1994) Nature 372, 798-800. Kyriakis, J.M. et al. (1994) Nature 369, 156-160. Park, H. et al. (2002) J. Biol. Chem. 277, 2573-2578.
Species
Homo Sapiens (Human)
Specificity
The antibody detects endogenous levels of total MAP2K4 protein.
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.
Pathway
ErbB signaling pathway MAPK signaling pathway TNF signaling pathway Fc epsilon RI signaling pathway Toll-like receptor signaling pathway
Protein Families
Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily
Tissue Specificity
Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.
Buffer
Supplied at 1.0mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Form
Supplied at 1.0mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Format
liquid
Purification
Antibodies were produced by immunizing rabbits with synthetic peptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific peptide.
Purity
Antibodies were produced by immunizing rabbits with synthetic peptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific peptide.
Storage
Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.