ROLE OF SAPK ERK KINASE-1 IN THE STRESS-ACTIVATED PATHWAY REGULATING TRANSCRIPTION FACTOR C-JUN/

THE stress-activated protein kinases (SAPKs), which are distantly rela ted to the MAP kinases, are the dominant c-Jun amino-terminal protein kinases activated in response to a variety of cellular stresses, inclu ding treatment with tumour-necrosis factor-a and interleukin-beta (ref s 1, 2). SAPK phosphorylation of c-Jun probably activates the c-Jun tr ansactivation function(3). SAPKs are part of a signal transduction cas cade related to, but distinct from, the MAPK pathway(1). We have now i dentified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), whi ch is structurally related to the MAP kinase kinases (MEKs)(4). SEK1 i s a potent activator of the SAPKs in vitro and in vivo. An inactive SE K1 mutant blocks SAPK activation by extracellular stimuli without inte rfering with the MAPK pathway. Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs , SEK1 further defines a signalling cascade that couples cellular stre ss agonists to the c-Jun transcription factor.