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

• In myotubes from insulin-resistant type II diabetic patients, siRNA against MAP4K4, MAP2K4, or MAP2K1 restored insulin action on glucose uptake to levels observed in healthy subjects [3].

Biological context of MAP4K4

• This protein kinase, designated HPK/GCK-like kinase (HGK), has nucleotide sequences that encode an open reading frame of 1165 amino acids with 11 kinase subdomains [4] .
• An even more interesting finding is that hesperetin suppressed NF-kappaB through four signal transduction pathways, NIK/IKK, ERK, p38, and JNK [5].

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