Fig. 8.

Working model on how aldosterone modulates NCC through both SPAK signaling pathway and DUSP6-dependent ERK1/2 signaling pathway. NCC within oval circle indicates NCC accumulation in plasma membrane which consists of NCC and phosphorylated NCC (pNCC). Majority of NCC pool are present in the cytoplasm. Long arrow lines indicate either activation of the kinases or direction of chemical reaction. Long broken arrow line indicates upregulation with unknown mechanism. A t-shaped line indicates inhibition effect. NCC-Ub indicates ubiquitinated NCC. pERK1/2 indicates phospho-ERK1/2. MEK is a MAP/ERK kinase, the upstream kinase of ERK1/2. DUSP6 is a dual-specificity protein phosphatase 6 (the specific ERK1/2 phosphatase).