Stress-Activated Protein Kinase

Feeling stressed from end-of-the-year obligations? You are not alone. We all have to deal with stress, even at the cellular level.

To maximize the probability of survival, cells need to coordinate their intracellular activities in response to changes in the extracellular environment. MAP kinase cascades play an important role in the transduction of signals inside eukaryotic cells. In particular, stress stimuli result in the rapid activation of a highly conserved group of MAP kinases, known as SAPKs (Stress-Activated Protein Kinases). These kinases coordinate the generation of adaptive responses that are essential for cell survival, which include the modulation of several aspects of cell physiology from metabolism to gene expression. Stress-activated protein kinases (SAPK)/Jun N-terminal kinases (JNK) are members of the MAPK family and are activated by a variety of environmental stresses, inflammatory cytokines, growth factors and GPCR agonists. Stress signals are delivered to this cascade by small GTPases of the Rho family (Rac, Rho, cdc42).

Confocal immunofluorescent analysis of HeLa cells untreated (left) and anisomycin-treated (right) using S0096-04C(green). Actin filaments have been labeled with DY554 phalloidin (red).

They require phosphorylation on tyrosine for phosphotransferase activity. SAP Kinase was originally shown to phosphorylate microtubule-associated protein-2, but c-Jun appears to be an important physiological target of this kinase. Consequently SAPK has also been called Jun Kinase. Phosphorylation of Ser-63 and Ser-73 of c-Jun by SAP kinases promotes activation of the transcription factor AP-1. cDNA cloning studies with rat and human libraries have shown that there are several isoforms of the SAP Kinase family. Many stimuli activate SAP Kinase, including heat shock, hyperosmotic shock, UV irradiation, exposure to protein synthesis inhibitors such as cycloheximide and anisomycin, and treatment with proinflammatory cytokines such as tumor necrosis factor-alpha.