Stresses

As the name implies, the SAPK and p38 MAPK pathways are potently activated by a wide variety of stresses and cellular insults. These include:

• heat shock
• UV irradiation
• inflammatory cytokines (such as TNF and IL-1)
• tunicamycin
• chemotherapeutic drugs (e.g. cisplatinum)
• anisomycin
• sorbitol/hyperosmolarity
• gamma irradiation
• sodium arsenite

The kinases are also induced by ischaemia (p38) or reperfusion following ischaemia (SAPK: Pombo CM, Bonventre JV, Woodgett JR, Kyriakis, JM and Force T (1994) The stress-activated protein kinases (SAPKs) are major c-Jun amino terminal kinases activated by ischemia and reperfusion. J. Biol. Chem. 269, 26546-26550).

Although SAPK and p38 share many agonists, their differential induction by ishaemia or reperfusion clearly indicates that the pathways can be independently regulated by distinct upstream components.