The functional presence of NHERF-1 was implicated in the late 1980s from a series of studies of inhibition of Na+/H+ exchange in rabbit kidney brush border membrane by cyclic AMP-dependent protein kinase (PKA). It took almost another decade before the cloning and molecular identification of NHERF-1 (Weinman et al. 1995). Shortly after, NHERF-2 was cloned from a yeast two-hybrid screen as an NHE3 interacting protein and was initially named E3KARP based on its ability to mediate PKA-dependent inhibition of Na+/H+ exchanger 3 (NHE3) in PS120 fibroblasts (Yun et al. 1997). NHERF-3 was initially identified as a protein that is upregulated in low dietary phosphate and was later shown to interact with the type II Na/Pi cotransporter (Npt2a) (Gisler et al. 2001). NHERF-4 was shown to interact with the...
This work was supported by the grant from the National Institutes of Health (DK071597 and DK061418).
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