Stress-activated protein kinase family

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). 

Fig. 13.2. TNFa receptor-signaling activates of all three members of the mitogen activated protein kinase (MARK) family, including the p44/p42 (also termed extracellular signal-related kinases, ERK-1/2), the c-Jun-NH2-terminal kinases (JNK also termed stress-activated protein kinases, SAPK), and p38 MARK (also termed stress/cytokine-activated kinases). U0126 blocks MARK kinase (MEK) phosphorylation of ERKl/2.

Mitogen-activated protein kinase (MAPK) p38o is a member of a family of Ser/Thr-spe-cific protein kinases that are activated upon exposure of cells to mitogens such as bacterial lipopolysaccharide or environmental stresses such as exposure to UV irradiation or chemical... 

---