Wang HR et al. - Mutagenesis studies revealed that charge-charge interactions between two conserved catalytic residues (Lys-233 and Asp-368) within the kinase domain (not the kinase activity) is critical for kinase domain to reverse the antagonism of NL domain. The WNK1 auto-inhibitory domain (AID; amino acids 491-555) also affected ROMK, presumably by modulating the kinase domain conformation. Thus, multiple intra- and/or intermolecular interactions of WNK1 domains are at play for regulation of ROMK1 by WNK1.
