RGD Reference Report - Identification of the WNK-SPAK/OSR1 signaling pathway in rodent and human lenses. - Rat Genome Database

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Identification of the WNK-SPAK/OSR1 signaling pathway in rodent and human lenses.

Authors: Vorontsova, I  Lam, L  Delpire, E  Lim, J  Donaldson, P 
Citation: Vorontsova I, etal., Invest Ophthalmol Vis Sci. 2014 Dec 16;56(1):310-21. doi: 10.1167/iovs.14-15911.
RGD ID: 11535087
Pubmed: PMID:25515571   (View Abstract at PubMed)
PMCID: PMC4294287   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.14-15911   (Journal Full-text)

PURPOSE: To identify whether the kinases that regulate the activity of cation chloride cotransporters (CCC) in other tissues are also expressed in rat and human lenses. METHODS: The expression of with-no-lysine kinase (WNK 1, 3, 4), oxidative stress response kinase 1 (OSR1), and Ste20-like proline alanine rich kinase (SPAK) were determined at either the transcript or protein levels in the rat and human lenses by reverse-transcriptase PCR and/or Western blotting, respectively. Selected kinases were regionally and subcellularly characterized in rat and human lenses. The transparency, wet weight, and tissue morphology of lenses extracted from SPAK knock-out animals was compared with wild-type lenses. RESULTS: WNK 1, 3, 4, SPAK, and OSR1 were identified at the transcript level in rat lenses and WNK1, 4, SPAK, and OSR1 expression confirmed at the protein level in both rat and human lenses. SPAK and OSR1 were found to associate with membranes as peripheral proteins and exhibited distinct subcellular and region-specific expression profiles throughout the lens. No significant difference in the wet weight of SPAK knock-out lenses was detected relative to wild-type lenses. However, SPAK knock-out lenses showed an increased susceptibility to opacification. CONCLUSIONS: Our results show that the WNK 1, 3, 4, OSR1, and SPAK signaling system known to play a role in regulating the phosphorylation status, and hence activity of the CCCs in other tissues, is also present in the rat and human lenses. The increased susceptibility of SPAK lenses to opacification suggests that disruption of this signaling pathway may compromise the ability of the lens to control its volume, and its ability to maintain its transparency.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell cortex located_inIDA 11535087; 11535087PMID:25515571ParkinsonsUK-UCL 
cytosol located_inIDA 11535087; 11535087; 11535087; 11535087PMID:25515571ParkinsonsUK-UCL 
membrane located_inIDA 11535087; 11535087PMID:25515571ParkinsonsUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Osr1  (odd-skipped related transcription factor 1)
Stk39  (serine threonine kinase 39)
Wnk1  (WNK lysine deficient protein kinase 1)
Wnk4  (WNK lysine deficient protein kinase 4)


Additional Information