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2013 ; 95
(6
): 1258-65
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gab.com Text
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English Wikipedia
The serum- and glucocorticoid-induced protein kinase-1 (Sgk-1) mitochondria
connection: identification of the IF-1 inhibitor of the F(1)F(0)-ATPase as a
mitochondria-specific binding target and the stress-induced mitochondrial
localization of endogenous Sgk-1
#MMPMID23402912
O'Keeffe BA
; Cilia S
; Maiyar AC
; Vaysberg M
; Firestone GL
Biochimie
2013[Jun]; 95
(6
): 1258-65
PMID23402912
show ga
The expression, localization and activity of the serum- and
glucocorticoid-induced protein kinase, Sgk-1, are regulated by multiple hormonal
and environmental cues including cellular stress. Biochemical fractionation and
indirect immunofluorescence demonstrated that sorbitol induced hyperosmotic
stress stimulated expression and triggered the localization of endogenous Sgk-1
into the mitochondria of NMuMG mammary epithelial cells. The immunofluorescence
pattern of endogenous Sgk-1 was similar to that of a green fluorescent linked
fusion protein linked to the N-terminal Sgk-1 fragment that encodes the
mitochondrial targeting signal. In the presence or absence of cellular stress,
exogenously expressed wild type Sgk-1 efficiently compartmentalized into the
mitochondria demonstrating the mitochondrial import machinery per se is not
stressed regulated. Co-immunoprecipitation and GST-pull down assays identified
the IF-1 mitochondrial matrix inhibitor of the F1F0-ATPase as a new Sgk-1 binding
partner, which represents the first observed mitochondrial target of Sgk-1. The
Sgk-1/IF-1 interaction requires the 122-176 amino acid region within the
catalytic domain of Sgk-1 and is pH dependent, occurring at neutral pH but not at
slightly acidic pH, which suggests that this interaction is dependent on
mitochondrial integrity. An in vitro protein kinase assay showed that the
F1F0-ATPase can be directly phosphorylated by Sgk-1. Taken together, our results
suggest that stress-induced Sgk-1 localizes to the mitochondria, which permits
access to physiologically appropriate mitochondrial interacting proteins and
substrates, such as IF-1 and the F1F0-ATPase, as part of the cellular stressed
induced program.