| First Author | Saritas T | Year | 2013 |
| Journal | J Am Soc Nephrol | Volume | 24 |
| Issue | 3 | Pages | 407-18 |
| PubMed ID | 23393317 | Mgi Jnum | J:358372 |
| Mgi Id | MGI:7780211 | Doi | 10.1681/ASN.2012040404 |
| Citation | Saritas T, et al. (2013) SPAK differentially mediates vasopressin effects on sodium cotransporters. J Am Soc Nephrol 24(3):407-18 |
| abstractText | 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. |
