MAP4K4 is a serine/threonine kinase that signals upstream of the c-Jun N-terminal kinase (JNK) and is involved in cell motility. MAP4K4 appears to partially mediate TNF alpha signaling. In skeletal muscle TNF-alpha induces insulin resistance. TNF-alpha induced insulin resistance has been shown to be dependent on MAPK4K4 activity. Interestingly, TNF-alpha regulates MAP4K4 expression and can stimulate MAP4K4 gene expression via TNFR2 (TNFalpha receptor 2) and the c-Jun and ATF2 (activating transcription factor 2) transcription factors. MAP4K4 is highly expressed in most tumor cell lines, and the analysis of MAP4K4 mutants indicates that it may have an important role in cell transformation and invasiveness.