AI Article Synopsis
- Changes in body fluid osmolality can be harmful to cells, and organisms have mechanisms to cope with this stress, though the specifics in mammals are not fully understood.
- The study reveals that ASK3, predominantly found in the kidneys, responds to osmotic stress by changing its kinase activity and interacts with WNK1, a protein associated with inherited hypertension.
- Knocking down ASK3 enhances the activation of the WNK1-SPAK/OSR1 signaling pathway, and ASK3 knockout mice show high blood pressure and increased SPAK/OSR1 activity, indicating ASK3's role as a regulator of blood pressure.
Article Abstract
Changes in the osmolality of body fluids pose a serious danger to cells and living organisms, which have developed cellular systems to sense and respond to osmotic stress and to maintain homoeostasis of body fluid. However, these processes are incompletely understood in mammals. Here we show that apoptosis signal-regulating kinase 3 (ASK3) is predominantly expressed in the kidney and alters its kinase activity bidirectionally in response to osmotic stress. We further demonstrate that ASK3 interacts with WNK1, mutation in which causes an inherited form of hypertension in humans. Knockdown of Ask3 by short interfering RNA enhances the activation of the WNK1-SPAK/OSR1 signalling pathway. Moreover, Ask3 knockout mice exhibit a hypertensive phenotype, in addition to hyperactivation of SPAK/OSR1 in renal tubules. Our results suggest that ASK3 is a unique bidirectional responder to osmotic stress and that it has a role in the control of blood pressure as an upstream suppressor of the WNK1-SPAK/OSR1 signalling pathway.
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| http://dx.doi.org/10.1038/ncomms2283 | DOI Listing |
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