Activation of the Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) and the Na(+)-Cl(-)-cotransporter (NCC) by vasopressin includes their phosphorylation at defined, conserved N-terminal threonine and serine residues, but the kinase pathways that mediate this action of vasopressin are not well understood. Two homologous Ste20-like kinases, SPS-related proline/alanine-rich kinase (SPAK) and oxidative stress responsive kinase (OSR1), can phosphorylate the cotransporters directly. In this process, a full-length SPAK variant and OSR1 interact with a truncated SPAK variant, which has inhibitory effects. Here, we tested whether SPAK is an essential component of the vasopressin stimulatory pathway. We administered desmopressin, a V2 receptor-specific agonist, to wild-type mice, SPAK-deficient mice, and vasopressin-deficient rats. Desmopressin induced regulatory changes in SPAK variants, but not in OSR1 to the same degree, and activated NKCC2 and NCC. Furthermore, desmopressin modulated both the full-length and truncated SPAK variants to interact with and phosphorylate NKCC2, whereas only full-length SPAK promoted the activation of NCC. In summary, these results suggest that SPAK mediates the effect of vasopressin on sodium reabsorption along the distal nephron.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582200PMC
http://dx.doi.org/10.1681/ASN.2012040404DOI Listing

Publication Analysis

Top Keywords

spak
9
mediates vasopressin
8
full-length spak
8
spak variant
8
truncated spak
8
spak variants
8
vasopressin
5
spak differentially
4
differentially mediates
4
vasopressin effects
4

Similar Publications

Calcium/calmodulin dependent protein kinase II inhibitor 1 (Camk2n1) is closely associated with a peak logarithm of odds score in quantitative trait loci for systolic blood pressure. Increased Camk2n1 mRNA expression has been specifically observed in the kidneys of hypertension mouse models. However, the precise role of Camk2n1 in the kidney remains unclear.

View Article and Find Full Text PDF
Article Synopsis
  • A team of over 180 researchers from more than 40 countries is addressing the issues related to "phantom agents," which are proposed pathogenic agents that are listed without concrete evidence of their existence.
  • These phantom agents, identified only through symptoms and lacking proper isolates or genetic data, create obstacles for trade and plant certification, making effective detection and risk assessment difficult.
  • The researchers recommend removing these agents from regulatory lists and updating standards in line with modern diagnostic methods to facilitate germplasm exchange and support global agriculture.
View Article and Find Full Text PDF

The evolving concepts of KS-WNK1 effect on NCC activity.

Am J Physiol Renal Physiol

December 2024

Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, 14080 Mexico.

The field of the with no lysine kinases (WNKs) regulation of the thiazide-sensitive NaCl cotransporter (NCC) began at the start of the century with the discovery that mutations in two members of the family, WNK1 and WNK4, resulted in a condition known as Familiar Hyperkalemic Hypertension (FHHt). Since FHHt is the mirror image of Gitelman's syndrome that is caused by inactivating mutations of the SLC12A3 gene encoding NCC, it was expected that WNKs modulated NCC activity and that the increased function of the cotransporter is the pathophysiological mechanism of FFHt. This turned out to be the case.

View Article and Find Full Text PDF

Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF-κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus.

CNS Neurosci Ther

October 2024

Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

Background: Hydrocephalus is characterized by secretion, circulation, and absorption disorder of cerebrospinal fluid (CSF) with high morbidity and complication rate. The relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) had received more attention. In this study, we aim to detect the role of Toll-like receptor 4/nuclear factor-kappa B/Na+/K+/2Cl-cotransporter 1(TLR4/NF-κB/NKCC1) signal pathway in the development of hydrocephalus.

View Article and Find Full Text PDF
Article Synopsis
  • The Erysimum latent virus (ELV) is a plant virus first discovered in wild and cultivated brassicas in Germany, distinct from the turnip yellow mosaic virus (TYMV).
  • ELV and TYMV were among the first plant viruses to have their genomes sequenced, with ELV identified as the likely ancestor of other tymoviruses.
  • The study includes the near-complete genomic sequence of an isolate from Czechia, showing it is closely related to the German isolates of ELV and belonging to the same virus species.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!