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1. Introduction
2. Signal transduction - a short introduction
3. Signal transduction resembles a wiring diagram
4. Protein phosphorylation and protein kinase
5. Diseases caused by mutations in protein kinases
6. WNK kinase mutations cause hypertension (1)
7. WNK kinase mutations cause hypertension (2)
8. Identification of WNK1-interacting proteins
9. SPAK and OSR1 are close relatives
10. WNK1 phosphorylates and activates SPAK & OSR1
11. CCT domain in SPAK/OSR1 binds WNK1
12. SPAK/OSR1 phosphorylation regulates NKCC1
13. CCT in SPAK/OSR1 also binds NKCC1 substrate
14. The CCT domain binds to an RFXV motif peptide
15. Conclusions (1)
16. Regulation of WNK1 by hyperosmotic conditions
17. Hyperosmotic stress activates NKCC1
18. Hyperosmotic stress - WNK1 & SPAK/OSR1
19. Hyperosmotic stress activates WNK1
20. How osmotic stress induces WNK1 activation
21. Phosphorylation sites in WNK1
22. Regulation of WNK1-SPAK/OSR1 interactions
23. Hyperosmotic stress activates SPAK/OSR1
24. Conclusions (2)
25. Thiazide diuretics affect blood pressure-model
26. Is NCC phosphorylated by WNK-SPAK pathway?
27. Analysis of NCC phosphorylation in mpkDCT cells
28. Thr60 phosphorylation mediates NCC activation
29. Summary (1)
30. Defining the physiological roles of SPAK in KI mice
31. Phosphorylation of NCC in the kidney in KI mice
32. Arterial blood pressure measurements
33. Reduced blood pressure in SPAK knock-in mice
34. Conclusions (3)
35. WNK1 and SPAK/OSR1 phosphorylate NKCC2
36. Roles of MO25 beyond regulating LKB1
37. STRADalpha interacts with MO25 (1)
38. STE20 kinase family tree
39. Effect of MO25 on 27 STE-kinases
40. SPAK/OSR1 phosphorylates NCC and NKCC2
41. MO25 enhances NKCC2/NCC phosphorylation
42. MO25 binds to STRAD via two sites (Sites 1/2)
43. Mutations in MO25 reduce SPAK activation
44. STRADalpha interacts with MO25 (2)
45. OSR1 activation by MO25
46. Summary (2)

Topics Covered

• Mutations in WNK kinases cause familial hypertension
• WNK1 interacts with and activates SPAK and OSR1
• Physiological functions of SPAK and OSR1
• Hyperosmotic conditions affect NKCC1 via WNK1 and SPAK/OSR1
• A suggested mechanism of action for Thiazide diuretics in Gordon's syndrome patients
• How the WNK pathway regulates blood pressure-a current model
• Defining physiological roles of SPAK in knock-in mice
• MO25 also regulates the activity of SPAK/OSR1
• Functions and schematic representation of LKB1 and SPAK/OSR1 protein complexes

Links

Series:

• Protein Phosphorylation

Categories:

• Biochemistry
• Clinical Practice

Therapeutic Areas:

• Cardiovascular & Metabolic

Talk Citation

Alessi, D. (2011, March 16). WNK1 pathway and its role in regulating hypertension [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved April 15, 2025, from https://doi.org/10.69645/AIBZ8759.
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Publication History

• Published on March 16, 2011

Financial Disclosures

• Prof. Dario Alessi has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.