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Cellular stress can result in dysfunction and disease, and mechanisms exist to combat this. Previously unknown steps have been uncovered in a pathway that signals when mitochondrial organelles are dysfunctional. Cleaved protein is a signal that activates the integrated stress response., Author(s): Bradford P. Tremblay, Cole M. Haynes Author Affiliations: Mitochondrial distress call moves to the cytosol to trigger a response to stress Organelles called mitochondria are responsible for storing energy [...]

A newly identified protein kinase, termed stress-activated protein-kinase (SAPK)/ERK kinase-1 (SEK1), mediates the in vitro and in vivo activation of the SAPKs, which are c-Jun amino-terminal protein kinases activated by cellular stresses. A structural relation exists between SEK1 and the MAP kinase kinases. SEK1 forms a signalling cascade that correlates cellular stress agonists and the c-Jun transcription factor. SAPK activation is inhibited by an inactive SEK1 mutant via extracellular stimuli and this action does not affect the MAPK pathway.

Analysis of NIH3T3 cell sublines expressing MEK kinase-1 (MEKK) shows that MEKK induction activates the stress-activated protein kinases (SAPKs). A new signalling cascade is regulated by MEKK upon phosphorylation of the SAPK activator, SEK1, which phosphorylates and stimulates SAPK. MEKK is similar to kinases mediating yeast mating signal cascades and is involved in vitro MEK activation.