Apoptosis signaling kinases: from stress response to health outcomes.

Apoptosis is a highly regulated process essential for the development and homeostasis of multicellular organisms. Whereas caspases, a large family of intracellular cysteine proteases, play central roles in the execution of apoptosis, other proapoptotic and antiapoptotic regulators such as the members of the Bcl-2 family are also critically involved in the regulation of apoptosis. A large body of evidence has revealed that a number of protein kinases are among such regulators and regulate cellular sensitivity to various proapoptotic signals at multiple steps in apoptosis. However, recent progress in the analysis of these apoptosis signaling kinases demonstrates that they generally act as crucial regulators of diverse cellular responses to a wide variety of stressors, beyond their roles in apoptosis regulation. In this review, we have cataloged apoptosis signaling kinases involved in cellular stress responses on the basis of their ability to induce apoptosis and discuss their roles in stress responses with particular emphasis on health outcomes upon their dysregulation.