The serine‐threonine kinase PIM3 is an aldosterone‐regulated protein in the distal nephron
| Autor: | Alain Doucet, Marc Maillard, Caroline Ronzaud, Lydie Cheval, Alessia Spirli, David Penton, Olivier Staub, Anne Debonneville, Johannes Loffing |
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| Přispěvatelé: | Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne (UNIL), Medical Cell Biology, Universität Regensburg (UR), University of Fribourg, University of Zurich, Staub, Olivier |
| Rok vydání: | 2019 |
| Předmět: |
Male
10017 Institute of Anatomy Physiology [SDV]Life Sciences [q-bio] 030204 cardiovascular system & hematology Plasma renin activity lcsh:Physiology chemistry.chemical_compound 2737 Physiology (medical) 0302 clinical medicine Aldosterone/pharmacology Animals Kidney/drug effects Kidney/metabolism Mice Inbred C57BL Nephrons/drug effects Nephrons/metabolism Nuclear Proteins/genetics Phenotype Protein-Serine-Threonine Kinases/metabolism Sodium/metabolism Transcription Factors/genetics Blood pressure blood volume kidney steroid hormone MESH: Sodium MESH: Animals Threonine Aldosterone Original Research Kidney lcsh:QP1-981 Chemistry Kinase Nuclear Proteins MESH: Transcription Factors Cell biology medicine.anatomical_structure Regulatory Pathways PIM1 610 Medicine & health Protein Serine-Threonine Kinases MESH: Phenotype MESH: Protein-Serine-Threonine Kinases 03 medical and health sciences MESH: Mice Inbred C57BL Physiology (medical) medicine MESH: Nephrons Serine/threonine-specific protein kinase Sodium MESH: Aldosterone Nephrons 1314 Physiology MESH: Kidney MESH: Male 570 Life sciences biology MESH: Nuclear Proteins 030217 neurology & neurosurgery Homeostasis Transcription Factors |
| Zdroj: | Physiological Reports Physiological Reports, Wiley, 2019, 7 (15), pp.e14177. ⟨10.14814/phy2.14177⟩ Physiological Reports, Vol 7, Iss 15, Pp n/a-n/a (2019) Physiological reports, vol. 7, no. 15, pp. e14177 |
| ISSN: | 2051-817X |
| DOI: | 10.14814/phy2.14177 |
| Popis: | The mineralocorticoid hormone aldosterone plays a crucial role in the control of Na + and K + balance, blood volume, and arterial blood pressure, by acting in the aldosterone-sensitive distal nephron (ASDN) and stimulating a complex transcriptional, translational, and cellular program. Because the complexity of the aldosterone response is still not fully appreciated, we aimed at identifying new elements in this pathway. Here, we demonstrate that the expression of the proto-oncogene PIM3 (Proviral Integration Site of Moloney Murine Leukemia Virus 3), a serine/threonine kinase belonging to the calcium/calmodulin-regulated group of kinases, is stimulated by aldosterone in vitro (mCCD cl1 cells), ex vivo (mouse kidney slices), and in vivo in mice. Characterizing a germline Pim3 - / - mouse model, we found that these mice have an upregulated Renin-Angiotensin-Aldosterone System (RAAS), with high circulating aldosterone and plasma renin activity levels on both standard or Na + -deficient diet. Surprisingly, we did not observe any obvious salt-losing phenotype in Pim3 KO mice as shown by normal blood pressure, plasma and urinary electrolytes, as well as unchanged expression levels of the major Na + transport proteins. These observations suggest that the potential effects of the loss of the Pim3 gene are physiologically compensated. Indeed, the 2 other family members of the PIM kinase family, PIM1 and PIM2 are upregulated in the kidney of Pim3 - / - mice, and may therefore be involved in such compensation. In conclusion, our data demonstrate that the PIM3 kinase is a novel aldosterone-induced protein, but its precise role in aldosterone-dependent renal homeostasis remains to be determined. |
| Databáze: | OpenAIRE |
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