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MAP4K4  -  mitogen-activated protein kinase kinase...

Homo sapiens

Synonyms: FLH21957, HEL-S-31, HGK, HPK/GCK-like kinase HGK, KIAA0687, ...
 
 
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Disease relevance of MAP4K4

  • MAP4K4 expression was also associated with higher frequency of recurrence/metastasis, larger tumor size, and increased number of positive lymph nodes (P<0.05) [1].
 

High impact information on MAP4K4

  • The effect of MAP4K4 on cellular migration was found to be mediated through c-Jun N-terminal kinase, independent of AP1 activation and downstream transcription [2].
  • A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase [2].
  • Further studies of the promigratory role of MAP4K4 showed that the knockdown of this transcript inhibited the migration of multiple carcinoma cell lines, indicating a broad role in cell motility and potently suppressed the invasion of SKOV-3 cells in vitro [2].
 

Associations of MAP4K4 with chemical compounds

 

Biological context of MAP4K4

 

Anatomical context of MAP4K4

  • An active role for this kinase in transformation was suggested by an inhibition of H-Ras(V12)-induced focus formation by expression of inactive, dominant-negative mutants of HGK in both fibroblast and epithelial cell lines [6].
  • We showed HGK to be highly expressed in most tumor cell lines relative to normal tissue [6].
  • To further validate our approach, we characterized the role of the protein kinase MAP4K4 that was identified in the screen. siRNA studies showed a role for MAP4K4 in antigen mediated T-cell responses in Jurkat and primary T-cells [7].
 

Other interactions of MAP4K4

  • Using the chromatin immunoprecipitation (ChIP) assays, we show that PRIMA-1 restored p53 DNA binding activity to the promoters of the proapoptotic genes such as Bax and PUMA, but inhibited the binding activity to the promoters of the MAP4K4 gene [8].
  • HGK also increased AP-1-mediated transcriptional activity in vivo [4] .
  • In addition, by analyzing multiple promoter elements using reporter assays, we have shown that MAP4K4 is implicated in the activation of the TNF-alpha promoter [7].
 

Analytical, diagnostic and therapeutic context of MAP4K4

  • Western blotting analysis showed that IkappaB kinases (IKKs) were expressed in RBL-2H3 cells but NIK was not [9].

 

References

  1. Expression of MAP4K4 is associated with worse prognosis in patients with stage II pancreatic ductal adenocarcinoma. Liang, J.J., Wang, H., Rashid, A., Tan, T.H., Hwang, R.F., Hamilton, S.R., Abbruzzese, J.L., Evans, D.B., Wang, H. Clin. Cancer Res. (2008) [Pubmed]
  2. A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase. Collins, C.S., Hong, J., Sapinoso, L., Zhou, Y., Liu, Z., Micklash, K., Schultz, P.G., Hampton, G.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. MAP4K4 gene silencing in human skeletal muscle prevents tumor necrosis factor-alpha-induced insulin resistance. Bouzakri, K., Zierath, J.R. J. Biol. Chem. (2007) [Pubmed]
  4. A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. Yao, Z., Zhou, G., Wang, X.S., Brown, A., Diener, K., Gan, H., Tan, T.H. J. Biol. Chem. (1999) [Pubmed]
  5. Modulation of the age-related nuclear factor-kappaB (NF-kappaB) pathway by hesperetin. Kim, J.Y., Jung, K.J., Choi, J.S., Chung, H.Y. Aging Cell (2006) [Pubmed]
  6. The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion. Wright, J.H., Wang, X., Manning, G., LaMere, B.J., Le, P., Zhu, S., Khatry, D., Flanagan, P.M., Buckley, S.D., Whyte, D.B., Howlett, A.R., Bischoff, J.R., Lipson, K.E., Jallal, B. Mol. Cell. Biol. (2003) [Pubmed]
  7. Functional identification of kinases essential for T-cell activation through a genetic suppression screen. Mack, K.D., Von Goetz, M., Lin, M., Venegas, M., Barnhart, J., Lu, Y., Lamar, B., Stull, R., Silvin, C., Owings, P., Bih, F.Y., Abo, A. Immunol. Lett. (2005) [Pubmed]
  8. PRIMA-1 induces apoptosis by inhibiting JNK signaling but promoting the activation of Bax. Wang, T., Lee, K., Rehman, A., Daoud, S.S. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  9. Effects of Cot expression on the nuclear translocation of NF-kappaB in RBL-2H3 cells. Chikamatsu, S., Furuno, T., Kinoshita, Y., Inoh, Y., Hirashima, N., Teshima, R., Nakanishi, M. Mol. Immunol. (2007) [Pubmed]
 
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