Hydrostatic Pressure Sensing by WNK kinases

• DOI: 10.1091/mbc.e23-03-0113
• Publication Date: 2023-08-16T16:28:01Z
• Authors: John M. Humphreys; Liliana R. Teixeira; Radha Akella; Haixia He; Ashari R. Kannangara; Kamil Sekulski; John Pleinis; Joanna Liwocha; Jenny Jiou; Kelly A. Servage; Kim Orth; Lukasz Joachimiak; Josep Rizo; Melanie H. Cobb; Chad A. Brautigam; Aylin R. Rodan; Elizabeth J. Gold...
• Keywords: Hydrostatic pressure

Previous study has demonstrated that the WNK kinases 1 and 3 are direct osmosensors consistent with their established role in cell-volume control. may also be regulated by hydrostatic pressure. Hydrostatic pressure applied to cells culture N2 gas or Drosophila Malpighian tubules centrifugation induces phosphorylation of downstream effectors endogenous WNKs. In vitro, autophosphorylation activity unphosphorylated kinase domain WNK3 (uWNK3) is enhanced a lesser extent than 190 kPa gas. measurably alters structure uWNK3. Data from size exclusion chromatography line multi-angle light scattering (SEC-MALS), SEC alone at different back pressures, analytical ultracentrifugation (AUC), NMR, chemical crosslinking indicate change oligomeric presence dimer monomer. The effects on related those seen osmolytes. Potential mechanisms activation uWNK3 relationships osmosensing discussed.