Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport.

ABSTRACT: The type II sodium-dependent phosphate cotransporter (NPT2A) mediates renal phosphate uptake. The NPT2A is regulated by parathyroid hormone (PTH) and fibroblast growth factor 23, which requires Na⁺/H⁺ exchange regulatory factor-1 (NHERF1), a multidomain PDZ-containing phosphoprotein. Phosphocycling controls the association between NHERF1 and the NPT2A. Here, we characterize the critical involvement of G protein-coupled receptor kinase 6A (GRK6A) in mediating PTH-sensitive phosphate transport by targeted phosphorylation coupled with NHERF1 conformational rearrangement, which in turn allows phosphorylation at a secondary site. GRK6A, through its carboxy-terminal PDZ recognition motif, binds NHERF1 PDZ1 with greater affinity than PDZ2. However, the association between NH

SUBMITTER: Vistrup-Parry M 

PROVIDER: S-EPMC8042174 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature