The ups and downs of MEK kinase interactions

MEK kinases (MEKKs) comprise a family of related serine-threonine protein k inases that regulate mitogen-activated protein kinase (MAPK) signalling pat hways leading to c-Jun NH2-terminal kinase (JNK) and p38 activation, induce d by cellular stress (e.g., UV and gamma irradiation, osmotic stress., heat shock, protein synthesis inhibitors), inflammatory cytokines (e.g., tumour necrosis factor alpha, TNF alpha and interleukin-1, IL1) and G protein-cou pled receptor agonists (e.g., thrombin). These stress-activated kinases hav e been implicated in apoptosis, oncogenic transformation, and inflammatory responses in various cell types. At present, the signalling events involvin g MEKKs are not well understood. This review summarises our current knowled ge concerning the regulation and function of MEKK family members, with part icular emphasis on those factors capable of directly interacting with disti nct MEKK isoforms. (C) 2001 Elsevier Science Inc. All rights reserved.