Clue to Switching Off the Cytokine Storm; Scientists Describe Architecture of Key Two-Kinase Complex That Acts As Final Switch to Trigger Inflammatory Response

Matthew Bowler, PhD

Constant exposure of cells to stressing agents, such as pathogens, may disturb an organism’s normal functioning. To fight stress, cells have developed several coping mechanisms, including the inflammatory response. While inflammation is necessary, too much of it can impair cell and organ function. This is the case with cytokine storms – inflammatory cascades during an infection that can spiral out of control and lead to severe disease and even death, as recently highlighted during the COVID-19 pandemic. In a new paper published September 14, 2023 in Science, EMBL Grenoble and University of Geneva researchers provide essential insights on a protein called p38α, belonging to the mitogen-activated protein kinase (MAPK) family, which is an important cellular “switch” triggering the inflammatory response. The scientists have obtained the first structure of p38α being activated by another regulatory protein kinase--MKK6--opening up new directions to develop drugs to stop cytokine storms. The Science article is titled “Architecture of the MKK6-p38α Complex Defines the Basis of MAPK Specificity and Activation.”

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