SAPKs stress-activated protein

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. 

The last step in the phosphorylation cascade involves the MAP kinases (mitogen-actirated protein kinases) or ERKs (extracellular signal-responsive kinases). There are two major kinds of MAP kinases the MAPKs and the JNKs (Jun N-terminal kinases Jun is a universal, growth-regulating transcription factor) or SAPKs (stress-activated protein kinases). There are six MAP kinases in yeast, and a number of mammalian MAP kinases have been cloned and more are to be expected. The MAP kinases are serine-threonine kinases and are actiwited by phosphorylation of a tyrosine and a threonine residue. 

INK (c-Jun N-terminal kinase) was first identified as the UV-induced activity responsible for phosphorylating, and thereby activating the proto-oncogene c-Jun (5). At the same time, they were found as SAPKs (stress-activated protein kinases), which are proline-directed kinases activated by growth factors and biosynthetic inhibitors such as anisomycin. Common stimuli that activate JNKs include inflammatory cytokines fatty acids and environmental stresses such as UV, osmotic shock, heat... 

SAPK stress-activated protein kinase (INK, MAPK8)... 

SAPK stress-activated protein kinase UP Ucr urine protein to creatinine ratio... 

Abbreviations PI3K, phosphoinositol-3-kinase GRK, G protein-coupled receptor kinase PLCp, phospholipase C-p SAPK, stress-activated protein kinase INK, c-Jun N-terminal kinase. 

Figure 9.5 Schematic representation of potential targets of CA-4 in endothelial cells P-MLC, phospho lated myosin light chain ERK, extracellular receptor kinase SAPK, stress-activated protein kinase [15]. (Reproduced with permission from Elsevier.)...

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). 

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. 

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... 

Two very similar groups of kinases with apparent molecular masses in the 46-57 kDa and 38 kDa ranges, respectively, were soon discovered in experiments with stressful stimuli such as the application of protein biosynthesis inhibitors or exposure of cells to (unphysiological) ultraviolet (UV) radiation (UVC <280 nm) [38] or lipopolysaccharide [39,40]. These stress-activated protein kinases (SAPK) are also proline-directed kinases that are activated by dual phosphorylation. The phosphorylation motif, however, differs from that of the classical MAPK, and is Thr-Pro-Tyr and Thr-Gly-Tyr, respectively, in the two SAPK groups. 

Park H-S, Park E, Kim M-S, et al. 2000. Selenite inhibits the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) through a thiol redox mechanism. J Biol Chem 275(4) 2527-2531. 

Cd has been shown to be a specific inducer of c-fos in mesangial cells through activation of Erk kinase, protein kinase C and stress-activated protein kinase (SAPK) pathways [223, 224] and may therefore also play a carcinogenic role in the kidney. 

---