Cell Signaling Technology

Product Pathways - MAPK Signaling

MEKK3 (D36G5) Rabbit mAb #5727

Applications Reactivity Sensitivity MW (kDa) Isotype
W IP H M R Mk Endogenous 78 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human  M=Mouse  R=Rat  Mk=Monkey
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

MEKK3 (D36G5) Rabbit mAb recognizes endogenous levels of total MEKK3 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro310 of human MEKK3 protein.

Western Blotting

Western Blotting

Western blot analysis of extracts from various cell types using MEKK3 (D36G5) Rabbit mAb.

Background

MAP kinase kinase kinase (MEKK3 or MAP3K3) is a serine/threonine protein kinase that activates SAPK and ERK via phosphorylation and activation of their respective MAP kinase kinases, SEK and MEK1/2 (1,2). MEKK3 also stimulates MEK5 via activation of ERK5/BMK1, which is at least partly regulated by a direct interaction between MEK5 and MEKK3 via p67phox-Bem1p (PB1) protein-protein interaction domains found in both proteins (3,4). MEKK3 modulates NF-κB activation in response to a variety of agonists including TNFα, LPS, IL-1 and LPA (5-9). Despite reports showing that phosphorylation of MEKK3 at Ser526 within the activation loop is necessary for kinase activation (10-12), at least one study suggests that dual phosphorylation at Thr516 and Ser520 is required for LPA-stimulated IKKβ/NF-κB activation (13). Phosphorylation at Thr294 appears to negatively regulate MEKK3 by promoting 14-3-3β binding and inhibition of the kinase activity (12). Phosphorylation of MEKK3 at Thr294 is diminished upon treatment of cells with LPS or TNFα, further suggesting an inhibitory role for this site (12).

  1. Blank, J.L. et al. (1996) J Biol Chem 271, 5361-8.
  2. Ellinger-Ziegelbauer, H. et al. (1997) J Biol Chem 272, 2668-74.
  3. Nakamura, K. and Johnson, G.L. (2003) J Biol Chem 278, 36989-92.
  4. Nakamura, K. et al. (2010) J Biol Chem 285, 2077-89.
  5. Yang, J. et al. (2001) Nat Immunol 2, 620-4.
  6. Zhao, Q. and Lee, F.S. (1999) J Biol Chem 274, 8355-8.
  7. Samanta, A.K. et al. (2004) J Biol Chem 279, 7576-83.
  8. Huang, Q. et al. (2004) Nat Immunol 5, 98-103.
  9. Sun, W. et al. (2009) Cell Signal 21, 1488-94.
  10. Zhang, D. et al. (2006) EMBO J 25, 97-107.
  11. Fritz, A. et al. (2006) J Biol Chem 281, 6236-45.
  12. Matitau, A.E. and Scheid, M.P. (2008) J Biol Chem 283, 13261-8.
  13. Sun, W. et al. (2010) J Biol Chem 285, 7911-18.

Application References

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Companion Products

For Research Use Only. Not For Use In Diagnostic Procedures.

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