Mitogen-activated protein (MAP) kinase cascades are activated by various extracellular stimuli including growth factors. The MEK kinases (also designated MAP kinase kinase kinases, MKKKs, MAP3Ks or MEKKs) phosphorylate and thereby activate the MEKs (also called MAP kinase kinases or MKKs), including ERK, JNK and p38. These activated MEKs in turn phosphorylate and activate the MAP kinases. The MEK kinases include Raf-1, Raf-B, Mos, MEK kinase-1, MEK kinase-2, MEK kinase-3, MEK kinase-4, ASK 1 (MEK kinase-5) and MAP3K6 (MEK kinase-6). MEK kinase-1 has been shown to phosphorylate MEK-1 via a Raf-independent pathway. Evidence suggests that MEK-3 is preferentially activated by MEK kinase-3 and that MEK-4 is activated by both MEK kinase-2 and MEK kinase-3. MEK kinase-4 has been shown to specifically activate the JNK pathway. ASK 1 activates both MEK-4 and MEK-3/MEK-6 pathways.
Background References
1. Mazur PK et al. SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature 510:283-7 (2014).
2. Brown RD et al. MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 304:H269-81 (2013).
Sequence Similarity
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Post-translational Modification
Autophosphorylated.; Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation.
Mitogen activated protein kinase kinase kinase 2 antibody
Mitogen-activated protein kinase kinase kinase 2 antibody
Images
Western blot analysis of MEKK2 on different lysates with Rabbit anti-MEKK2 antibody (ET1610-70) at 1/2,000 dilution.
Lane 1: Hep G2 (Human hepatocellular carcinoma cell) Lane 2: Rat brain tissue lysate
Lysates/proteins at 10 µg/Lane. Exposure time: 59 seconds; ECL: K1801
Blocking: 5% NFDM/TBST, 1 hour at room temperature Primary antibody: ET1610-70, 1/2,000 in primary antibody dilution buffer (K1803), overnight at 4 ℃ Secondary antibody: Goat anti-Rabbit IgG-HRP (HA1001), 1/50,000 in 5% NFDM/TBST, 1 hour at room temperature
Predicted band size: 70 kDa Observed band size: 70 kDa
☑ Knockout (KO)
All lanes: Western blot analysis of MEKK2 with anti-MEKK2 antibody [SC68-02] (ET1610-70) at 1:1,000 dilution. Lane 1: Wild-type HEK293A whole cell lysate (20 µg). Lane 2: MEKK2 knockout HEK293A whole cell lysate (20 µg). Lane 3: Wild-type MBMEC whole cell lysate (20 µg). Lane 4: MEKK2 knockout MBMEC whole cell lysate (20 µg).
ET1610-70 was shown to specifically react with MEKK2 in Wild-type HEK293A and Wild-type MBMEC cells. No band was observed when MEKK2 knockout samples were tested. Wild-type and MEKK2 knockout samples were subjected to SDS-PAGE. Proteins were transferred to a PVDF membrane and blocked with 5% NFDM in TBST for 1 hour at room temperature. The primary Anti-MEKK2 antibody (ET1610-70, 1/1,000) and Anti-β-actin antibody (R1207-1, 1/1,000) were used in 5% BSA at room temperature for 2 hours. Goat Anti-Rabbit IgG H&L (HRP) Secondary Antibody (HA1001) at 1:200,000 dilution was used for 1 hour at room temperature.
Immunohistochemical analysis of paraffin-embedded human breast carcinoma tissue using anti-MEKK2 antibody. Counter stained with hematoxylin.
Immunohistochemical analysis of paraffin-embedded mouse brain tissue using anti-MEKK2 antibody. Counter stained with hematoxylin.
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