Inhibition of WNK Kinases in NK Cells Disrupts Cellular Osmoregulation and Control of Tumor Metastasis.

ABSTRACT:

Introduction

The serine/threonine with-no-lysine (WNK) kinase family function in blood pressure control, electrolyte homeostasis, and cellular osmoregulation. These kinases and their downstream effectors are considered promising therapeutic targets in hypertension and stroke. However, the role of WNK kinases in immune cells remains poorly understood.

Methods

Using the small-molecule WNK kinase inhibitors WNK463 and WNK-IN-11, we investigated how WNK kinase inhibition affects natural killer (NK) cell physiology.

Results

WNK kinase inhibition with WNK463 or WNK-IN-11 significantly decreased IL-2-activated NK cell volume, motility, and cytolytic activity. Treatment of NK cells with these inhibitors induced autophagy by activating AMPK and inhibiting mTOR signaling. Moreo

SUBMITTER: Kim JS 

PROVIDER: S-EPMC11521464 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature