Abstract | BACKGROUND: METHODS AND RESULTS: RP-220 is a previously identified, 20 amino acids long renalase peptide that is devoid of any intrinsic enzymatic activity, but it is equally effective as full-length recombinant renalase at protecting against toxic and ischemic injury. Using biotin transfer studies with RP-220 in the human proximal tubular cell line HK-2 and protein identification by mass spectrometry, we identified PMCA4b as a renalase binding protein. This previously characterized plasma membrane ATPase is involved in cell signaling and cardiac hypertrophy. Co-immunoprecipitation and co-immunolocalization confirmed protein- protein interaction between endogenous renalase and PMCA4b. Down-regulation of endogenous PMCA4b expression by siRNA transfection, or inhibition of its enzymatic activity by the specific peptide inhibitor caloxin1b each abrogated RP-220 dependent MAPK signaling and cytoprotection. In control studies, these maneuvers had no effect on epidermal growth factor mediated signaling, confirming specificity of the interaction between PMCA4b and renalase. CONCLUSIONS: PMCA4b functions as a renalase receptor, and a key mediator of renalase dependent MAPK signaling.
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Authors | Ling Wang, Heino Velazquez, John Chang, Robert Safirstein, Gary V Desir |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 4
Pg. e0122932
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 25906147
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Epidermal Growth Factor
- Monoamine Oxidase
- renalase
- Mitogen-Activated Protein Kinases
- ATP2B4 protein, human
- Plasma Membrane Calcium-Transporting ATPases
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Topics |
- Acute Kidney Injury
(genetics, metabolism)
- Cell Line
- Cytoprotection
(genetics)
- Down-Regulation
(genetics)
- Epidermal Growth Factor
(genetics, metabolism)
- Essential Hypertension
- Humans
- Hypertension
(metabolism)
- Mitogen-Activated Protein Kinases
(genetics, metabolism)
- Monoamine Oxidase
(genetics, metabolism)
- Plasma Membrane Calcium-Transporting ATPases
(genetics, metabolism)
- Polymorphism, Single Nucleotide
(genetics)
- Protein Interaction Domains and Motifs
(genetics)
- Signal Transduction
(genetics)
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