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Abstract
MEK kinases (MEKKs) comprise a family of related serine-threonine protein kinases
that regulate mitogen-activated protein kinase (MAPK) signalling pathways leading
to c-Jun NH2-terminal kinase (JNK) and p38 activation, induced by cellular stress
(e.g., UV and gamma irradiation, osmotic stress, heat shock, protein synthesis inhibitors),
inflammatory cytokines (e.g., tumour necrosis factor alpha, TNFalpha, and interleukin-1,
IL1) and G protein-coupled receptor agonists (e.g., thrombin). These stress-activated
kinases have been implicated in apoptosis, oncogenic transformation, and inflammatory
responses in various cell types. At present, the signalling events involving MEKKs
are not well understood. This review summarises our current knowledge concerning the
regulation and function of MEKK family members, with particular emphasis on those
factors capable of directly interacting with distinct MEKK isoforms.