Aldosterone rapidly activates Src kinase in M-1 cells involving the mineralocorticoid receptor and HSP84.
We investigated the effect of aldosterone on Src kinase. In the kidney cell line, M-1 aldosterone leads to a >2-fold transient activation of Src kinase seen as early as 2 min after aldosterone administration. Maximal Src kinase activation was measured at an aldosterone concentration of 1 nM. In parallel to activation, autophosphorylation at Tyr-416 of Src kinase increased. Src kinase activation was blocked by spironolactone. Aldosterone led to increased association of Src with HSP84. Furthermore, rapamycin blocked aldosterone-induced Src activation. We conclude that Src activation by aldosterone is mediated through the mineralocorticoid receptor and HSP84.
Braun
Sabine
S
Department of Clinical Pharmacology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Lösel
Ralf
R
Wehling
Martin
M
Boldyreff
Brigitte
B
D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011233:Precipitin Tests; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013148:Spironolactone / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry; D019061:src-Family Kinases / Q000378:metabolism*
C488983:HSP84 protein, mouse; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D014443:Tyrosine; D000450:Aldosterone; D019061:src-Family Kinases; D020123:Sirolimus