Diversity and versatility of p38 kinase signalling in health and disease

The ability of cells to deal with different types of stressful situations in a precise and coordinated manner is key for survival and involves various signalling networks. Over the past 25 years, p38 kinases - in particular, p38 alpha - have been implicated in the cellular response to stress at many levels. These span from environmental and intracellular stresses, such as hyperosmolarity, oxidative stress or DNA damage, to physiological situations that involve important cellular changes such as differentiation. Given that p38 alpha controls a plethora of functions, dysregulation of this pathway has been linked to diseases such as inflammation, immune disorders or cancer, suggesting the possibility that targeting p38 alpha could be of therapeutic interest. In this Review, we discuss the organization of this signalling pathway focusing on the diversity of p38 alpha substrates, their mechanisms and their links to particular cellular functions. We then address how the different cellular responses can be generated depending on the signal received and the cell type, and highlight the roles of this kinase in human physiology and in pathological contexts. p38 alpha - the best-characterized member of the p38 kinase family - is a key mediator of cellular stress responses. p38 alpha is activated by a plethora of signals and functions through a multitude of substrates to regulate different cellular behaviours. Understanding context-dependent p38 alpha signalling provides important insights into p38 alpha roles in physiology and pathology.

Automated summary

The ability of cells to cope with various stressful situations is crucial for survival, with p38 alpha kinase playing a key role in the cellular stress response. Understanding the diversity of p38 alpha substrates, their mechanisms, and their connections to specific cellular functions is important for insights into physiology and pathology. Dysregulation of the p38 alpha pathway has been linked to diseases such as inflammation, immune disorders, and cancer.