Proposed model of how TCR/CD28 signals via WNK1, OXSR1 and STK39, via unknown ion transporters (possibly SLC12A-family), lead to ion influx and subsequent water entry through AQP3 by osmosis, which is required for TCR/CD28 signaling and T cell proliferation. Water entry is required for early TCR signaling and for the transition from G0 to G1. In addition, the WNK1 pathway inhibits ATR and thereby allows cells to transit the G2/M checkpoint. WNKi, WNK inhibitor (WNK463). Each point represents a different mouse; columns show median. Data pooled from 2 ( c ) or from 1 experiment representative of >2 ( a, b ) experiments. Statistical analysis carried out using the 2-sided Mann-Whitney U test. ns, not significant; * 0.01 < p < 0.05; ** 0.001 < p < 0.01; *** 0.0001 < p < 0.001; **** p < 0.0001. Image of cell cycle created in Biorender. Tybulewicz, V. (2024) https://BioRender.com/k55d532 . Source data are provided as a Source Data file.
