Protein kinases stress-activated

SAPK/JNK pathway. Within the SAPK (stress-activated protein kinase) class, the Jun NT-terminal kinases (JNKs) form a subfamily (SAPK/JNK 1-3). 

CDK, cyclin-dependent kinase ERK, extracellular signal-regulated kinase GRK, G protein receptor kinase JNK, Jun kinase MAP kinase, mitogen activated protein kinase MEK, MAP kinase and ERK kinases RSK, ribosomal S6 kinase, GSK, glycogen synthase kinase SAPK, stress-activated protein kinase SEK, SAPK kinase. 

A second family of MAPKs is referred to as stress-activated protein kinases (SAPKs) [3,14,15]. This includes JNKs, or Jun kinases, named originally for their phosphorylation of the transcription factor c-Jun. SAPKs were first identified in peripheral tissues on the basis of their activation in response to cellular forms of stress, which include X-ray irradiation and osmotic stress. More recently, they have been demonstrated to be activated in brain by several cytokines as well as by synaptic activity [16]. As shown in Figure 23-3, SAPKs are activated by SAPK kinases (SEKs), which are in turn activated by SEK kinases. The Ras-like small G proteins implicated in SEK kinase activation are Rac and Cdc-42. In this case, it appears that Rac/Cdc-42 triggers activation of SEK kinase by stimulating its phosphorylation by still another protein kinase termed p21-activated kinase (PAK). Thus, PAK can be considered a MAPK kinase kinase kinase, which is analogous to the cascade of protein kinases found in yeast (Fig. 23-4). 

PRA protein kinase A SAPR stress-activated protein kinase... 

Iordanov, M. S. et al. Ribotoxic stress response Activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA. Mol. Cell. Biol. 17, 3373, 1997. 

Shi, C. S. and J. H. Kehel, Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex Ubcl3-UevlA/TNF receptor-associated factor 2 (TRAF2). J Biol Chem, 2003, 278(17), 15429-34. 

Coroneos, E., Wang, Y., Panuska, J.R., Temepleton, D.J. and Kester, M., 1996, Sphingohpid metabolites differentially regulate extracellular signal-regulated kinase and stress-activated protein kinase cascades, B/oclrem. J. 316 13-17. 

G5. Graves, J. D., Draves, K. E., Craxton, A., Saklatvala, J., Krebs, E. G., and Clark, E. A., Involvement of stress-activated protein kinase and p38 mitogen-activated protein kinase in mIgM-induced apoptosis of human B lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 93, 13814— 13818 (1996). 

Okubo, Y., Blakesley, V. A., Stannard, B., Gutkind, S., and LeRoith, D., Insulin-like growth factor 1 inhibits the stress-activated protein kinase—Jun N-terminal kinase. J. Biol. Chem. 273, 25961-25966 (1998). 

Roselli. Saw palmetto extract sup- SR058 presses insulin-like growth fact or-1 signaling and induces stress-activated protein kinase/c-]un N-terminal kinase phosphorylation in human prostate epithelial cells. Endocrinology... 

An important subgroup of MAP kinases has the transcription factor c-Jun as substrate. These kinases are known as c-Jun NH2 terminal kinases (INK) or, due to their activation by stress signals, as stress activated protein kinases (SAPK). The JNK/SAPK proteins are part of their own protein kinase module that conducts stress signals further at the transcription level, and this signaling pathway is therefore known as the JNK/ SAPK pathway. 

C-Jun-N-terminal kinases The JNK/Stress-activated protein kinases (SAPKs) do not respond well to mitogens but are strongly activated by agents that induce cellular stress. These kinases phosphorylate C-Jun transcription factor. The sequence of the tripeptide motif for JNK is Thr-Pro-Tyr. The activators of cytokine and tyrosine kinase receptors transduce signal to the upstream MAPKKKs. These... 

Zinck, R., M.A. Cahill, M. Kracht, C. Sachsenmaier, R.A. Hipskind, and A. Nordheim. 1995. Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1. Mol. Cell Biol. 15 4930-4938. 

Force, T., Pombo, C.M., Avruch, J.A., Bonventre, J.V., and Kyriakis, J.M. 1996. Stress-activated protein kinases in cardiovascular disease. Circ Res 78 947-953. 

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