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MAP4K5  -  mitogen-activated protein kinase kinase...

Homo sapiens

Synonyms: GCKR, KHS, KHS1, Kinase homologous to SPS1/STE20, MAPK/ERK kinase kinase kinase 5, ...
 
 
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Disease relevance of MAP4K5

  • In this study, we isolated various HSV-1 strains, named KHS, from the skin lesions of Korean patients and characterized the specific features of each strain [1].
 

High impact information on MAP4K5

  • In addition, we show that GCKR positively affects the beta-catenin pathway in B cells [2].
  • Reduction of GCKR expression inhibits Wnt3a-induced phosphorylation of GSK3beta at serine 9 and decreases the accumulation of cytosolic beta-catenin [2].
  • Finally, we showed impairment of the known ability of CrkL to activate the SAPK pathway by a catalytically inactive form of GCKR or by a GCKR antisense construct [3].
  • Furthermore, in the Bcr-Abl transformed cell line, K562 endogenous GCKR and CrkL coimmunoprecipitated, indicating a constitutive association [3].
  • Here, we report that Bcr-Abl through a Ras-dependent pathway signals the serine/threonine protein kinase GCKR (Germinal Center Kinase Related) leading to SAPK activation [4].
 

Biological context of MAP4K5

  • These results make it likely that HPK1 and KHS participate in the signal transduction of Crk family adapter proteins in certain cell types [5].
  • Parental ONYX-411 or ONYX-411-siRNA(GFP) was markedly less effective (47.8% growth reduction, P = 0.03; and 44.1% growth reduction, P = 0.03, respectively). siRNA(ras) transgene activity contributed to cell cycle blockage, increased apoptosis, and marked down-regulation of Ras signaling-related gene expression (AKT2, GSK3beta, E2F2, and MAP4K5) [6].
  • No difference was found between the two groups in the distribution of three genotypes on MAP4K5 -822G/A [7].
  • The -822G/A polymorphism in the promoter region of the MAP4K5 gene is associated with reduced risk of type 2 diabetes in Chinese Hans from Shanghai [7].
  • The association between SNPs of MAP4K5 and type 2 diabetes (T2DM) was investigated due to the known relationship of the JNK pathway with T2DM [7].
 

Anatomical context of MAP4K5

  • The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins [5].
  • Our findings demonstrate that GCKR facilitates both canonical and noncanonical Wnt signaling in B lymphocytes [2].
  • Consistent with GCKR being a functional target in CML, GCKR is constitutively active in CML cell lines and found in association with Bcr-Abl [4].
  • We found that KHS strains produced small, cell associated and nonsyncycial plaques in Vero cells [1].
  • We also found that KHS 1 has a higher neurotropic affinity by determining the time it took for the virus to reach the trigerminal ganglia from the eyes [1].
 

Analytical, diagnostic and therapeutic context of MAP4K5

References

  1. Isolation of the enhanced neurovirulent HSV-1 strains from Korean patients. Kim, J.K., Kim, Y.K., Hong, J., Kim, S.Y., Lee, C.K., Kim, C.J., Kim, Y.S., Ahn, J.K. Virus Genes (2003) [Pubmed]
  2. The mitogen-activated protein kinase kinase kinase kinase GCKR positively regulates canonical and noncanonical Wnt signaling in B lymphocytes. Shi, C.S., Huang, N.N., Harrison, K., Han, S.B., Kehrl, J.H. Mol. Cell. Biol. (2006) [Pubmed]
  3. Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation. Shi, C.S., Tuscano, J., Kehrl, J.H. Blood (2000) [Pubmed]
  4. GCKR links the Bcr-Abl oncogene and Ras to the stress-activated protein kinase pathway. Shi, C.S., Tuscano, J.M., Witte, O.N., Kehrl, J.H. Blood (1999) [Pubmed]
  5. The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins. Oehrl, W., Kardinal, C., Ruf, S., Adermann, K., Groffen, J., Feng, G.S., Blenis, J., Tan, T.H., Feller, S.M. Oncogene (1998) [Pubmed]
  6. Antitumor activity of an oncolytic adenovirus-delivered oncogene small interfering RNA. Zhang, Y.A., Nemunaitis, J., Samuel, S.K., Chen, P., Shen, Y., Tong, A.W. Cancer Res. (2006) [Pubmed]
  7. The -822G/A polymorphism in the promoter region of the MAP4K5 gene is associated with reduced risk of type 2 diabetes in Chinese Hans from Shanghai. Gu, Y., Luo, T., Yang, J., Zhang, D., Dai, M., Jian, W., Zheng, S., Zhou, W., Zhou, W., Wu, Y., Liu, Y., Liu, Y., Li, J., Xie, X., Li, G., Luo, M. J. Hum. Genet. (2006) [Pubmed]
 
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