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Protein kinase D stabilizes aldosterone‐induced ERK1/2 MAP kinase activation in renal M1 cortical collecting duct cells to promote cell proliferation
Author(s) -
Dooley Ruth,
Harvey Brian J,
Thomas Warren
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.812.21
Subject(s) - aldosterone , protein kinase c , kinase , cell growth , microbiology and biotechnology , pkd1 , chemistry , protein kinase a , medicine , endocrinology , biology , kidney , biochemistry , polycystic kidney disease
Aldosterone rapidly stimulates ERK1/2 MAP kinase and this activation is stabilised via protein kinase D1 in M1 cells (1). Here we describe a novel effect of aldosterone on renal cell growth modulated by the ERK1/2 – PKD1 pathway. Aldosterone (10nM) promoted the growth of M1 cells over 48hr, an effect that was PKD1, PKCδ and ERK1/2‐dependent. This increase in cell growth was a result of stimulated proliferation and not due to suppression of apoptosis or necrosis. Aldosterone induced the rapid activation of ERK1/2 with peaks of activation at 2min and 10–30min, followed by sustained activation lasting >120min. Aldosterone promoted the association of PKD1 with ERK1/2 within 2min. M1 cells suppressed in PKD1 expression using siRNA exhibited only the early transient peaks in ERK1/2 activation without the sustained phase. Furthermore, aldosterone induced the subcellular redistribution of ERK1/2 to nuclei at 2min and to cytoplasmic sites proximal to the nuclei at 30min as measured using immunofluorescence confocal microscopy. The redistribution of ERK1/2 was inhibited in PKD1 knockdown cells. The stabilization of ERK1/2 activation and subcellular redistribution by PKD1 are required for aldosterone‐induced cell proliferation. Funded by Wellcome Trust, Higher Education Authority of Ireland PRTLI and Science Foundation Ireland RFP grants.