Parathyroid hormone initiates dynamic NHERF1 phosphorylation cycling and conformational changes that regulate NPT2A-dependent phosphate transport.

ABSTRACT: Na⁺-H⁺ exchanger regulatory factor-1 (NHERF1) is a PDZ protein that scaffolds membrane proteins, including sodium-phosphate co-transport protein 2A (NPT2A) at the plasma membrane. NHERF1 is a phosphoprotein with 40 Ser and Thr residues. Here, using tandem MS analysis, we characterized the sites of parathyroid hormone (PTH)-induced NHERF1 phosphorylation and identified 10 high-confidence phosphorylation sites. Ala replacement at Ser⁴⁶, Ser¹⁶², Ser¹⁸¹, Ser²⁶⁹, Ser²⁸⁰, Ser²⁹¹, Thr²⁹³, Ser²⁹⁹, and Ser³⁰² did not affect phosphate uptake, but S290A substitution abolished PTH-dependent phosphate transport. Unexpectedly, Ser²⁹⁰ was rapidly dephosphorylated and rephosp

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC6433080 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature