What question did this study set out to answer?

To determine the role of Thr95 phosphorylation in the first PDZ domain of NHERF-1 during parathyroid hormone- and dopamine-regulated renal phosphate transport.

June 23, 2010Journal of Biological ChemistryOpen Access

Cooperativity between the Phosphorylation of Thr95 and Ser77 of NHERF-1 in the Hormonal Regulation of Renal Phosphate Transport

View Full Paper

Ask AI

Bookmark

Authors

EWEdward J. WeinmanUniversity of Maryland, Baltimore DSDeborah SteplockWest Virginia University YZYinghua ZhangNortheast Agricultural University

Discussion

Member takes

Implication

Experimental study demonstrates cooperative phosphorylation of NHERF-1 in renal proximal tubule cells, indicating a coordinated mechanism for hormone-mediated phosphate transport inhibition.

Key Points

To determine the role of Thr95 phosphorylation in the first PDZ domain of NHERF-1 during parathyroid hormone- and dopamine-regulated renal phosphate transport.
Assayed in vitro phosphorylation of NHERF-1 Ser77 by PKC using a site-directed alanine substitution at position 95 (T95A).
Measured sodium-dependent phosphate uptake in NHERF-1-null proximal tubule cells transduced with adenoviruses expressing wild-type or T95A mutant NHERF-1 after treatment with parathyroid hormone or dopamine.
Quantified binding kinetics between Npt2a and phosphomimetic mutant NHERF-1 PDZ I domains (S77D and T95D) using surface plasmon resonance.
The T95A mutation markedly reduced both the rate and extent of Ser77 phosphorylation by PKC in vitro and prevented hormone-mediated inhibition of phosphate transport in cell models.
Surface plasmon resonance demonstrated that the phosphomimetic S77D mutation significantly reduced binding affinity to Npt2a, whereas the T95D mutation had no direct effect on transporter binding.
Both parathyroid hormone and dopamine enhanced the phosphorylation of Thr95, demonstrating that Thr95 phosphorylation primes subsequent Ser77 phosphorylation and transporter dissociation.

Cite This Study

Weinman et al. (2010) studied this question.

synapsesocial.com/papers/6a706d4b87f921057127abfe https://doi.org/10.1074/jbc.m110.132423

View Full Paper

Ask AI

Bookmark

Implication

Experimental study demonstrates cooperative phosphorylation of NHERF-1 in renal proximal tubule cells, indicating a coordinated mechanism for hormone-mediated phosphate transport inhibition.

Cooperativity between the Phosphorylation of Thr95 and Ser77 of NHERF-1 in the Hormonal Regulation of Renal Phosphate Transport

Discussion

Member takes

Implication

Key Points

Cite This Study

Cooperativity between the Phosphorylation of Thr95 and Ser77 of NHERF-1 in the Hormonal Regulation of Renal Phosphate Transport

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider