Cell Signaling Technology

Product Pathways - MAPK Signaling

DUSP4/MKP2 (D9A5) Rabbit mAb #5149

Applications Reactivity Sensitivity MW (kDa) Isotype
W H Mk Endogenous 42 Rabbit

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human  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

DUSP4/MKP2 (D9A5) Rabbit mAb recognizes endogenous levels of total DUSP4 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro168 of human DUSP4 protein.

Western Blotting

Western Blotting

Western blot analysis of extracts from various cell lines using DUSP4/MKP2 (D9A5) Rabbit mAb (upper) or GAPDH (D16H11) XP® Rabbit mAb #5174 (lower).

Background

MAP kinases are inactivated by dual-specificity protein phosphatases (DUSPs) that differ in their substrate specificity, tissue distribution, inducibility by extracellular stimuli, and cellular localization. DUSPs, also known as MAPK phosphatases (MKP), specifically dephosphorylate both threonine and tyrosine residues in MAPK P-loops and have been shown to play important roles in regulating the function of the MAPK family (1,2). At least 13 members of the family (DUSP1-10, DUSP14, DUSP16, and DUSP22) display unique substrate specificities for various MAP kinases (3). MAPK phosphatases typically contain an amino-terminal rhodanese-fold responsible for DUSP docking to MAPK family members and a carboxy-terminal catalytic domain (4). These phosphatases can play important roles in development, immune system function, stress responses, and metabolic homeostasis (5). In addition, research studies have implicated DUSPs in the development of cancer and the response of cancer cells to chemotherapy (6).

DUSP4 (MKP2, hVH2) is a nuclear dual-specificity phosphatase that is a negative regulator of Erk1/2 signaling by dephosphorylating and inactivating Erk1/2 in response to growth factors (7,8). Treatment with mitogen or expression of activating mutations of Ras (G12V) or Raf (V600E) promote increased expression of DUSP4 and a coincident decrease in phospho-Erk in the nucleus (9). In contrast, numerous studies have detected decreased expression of DUSP4 in a variety of tumor types, resulting in increased signaling via the Ras/Erk pathway, enhanced tumor growth, and decreased drug sensitivity (10-12). DUSP4/MKP2 also plays an important role in regulating the immune system where it has been implicated in regulating T and B cell proliferation and apoptosis, and adaptive and inflammatory responses (13-16).

  1. Camps, M. et al. (2000) FASEB J 14, 6-16.
  2. Theodosiou, A. and Ashworth, A. (2002) Genome Biol 3, REVIEWS3009.
  3. Salojin, K. and Oravecz, T. (2007) J Leukoc Biol 81, 860-9.
  4. Tanoue, T. et al. (2002) J Biol Chem 277, 22942-9.
  5. Dickinson, R.J. and Keyse, S.M. (2006) J Cell Sci 119, 4607-15.
  6. Wu, G.S. (2007) Cancer Metastasis Rev 26, 579-85.
  7. Peng, D.J. et al. (2010) Cell Cycle 9, 4650-5.
  8. Lawan, A. et al. (2011) J Biol Chem 286, 12933-43.
  9. Cagnol, S. and Rivard, N. (2012) Oncogene , .
  10. Chitale, D. et al. (2009) Oncogene 28, 2773-83.
  11. Waha, A. et al. (2010) Cancer Res 70, 1689-99.
  12. Balko, J.M. et al. (2012) Nat Med 18, 1052-9.
  13. Ramesh, S. et al. (2008) EMBO Rep 9, 990-7.
  14. Cornell, T.T. et al. (2010) Infect Immun 78, 2868-76.
  15. Huang, C.Y. et al. (2012) Eur J Immunol 42, 476-88.
  16. Yu, M. et al. (2012) Proc Natl Acad Sci U S A 109, E879-88.

Application References

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

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