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Serum‐ and glucocorticoid‐dependent kinase‐1‐induced cell migration is dependent on vinculin and regulated by the membrane androgen receptor
Author(s) -
Schmidt EvaMaria,
Gu Shuchen,
Anagnostopoulou Vasileia,
Alevizopoulos Konstantinos,
Föller Michael,
Lang Florian,
Stournaras Christos
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2012.08515.x
Subject(s) - vinculin , sgk1 , microbiology and biotechnology , transfection , biology , cell migration , kinase , phosphorylation , chemistry , cell , focal adhesion , cell culture , biochemistry , genetics
The serum‐ and glucocorticoid‐dependent kinases 1–3 (SGK1–3) are downstream effectors of phosphatidylinositol 3‐kinases, implicated in various cell responses including colon cancer tumorigenesis in mice. Here, we investigated the role of SGK1 in the regulation of cell motility. Using Caco‐2 colon tumor and HEK293 embryonic kidney cells, we report that transfection with the constitutively active SGK1 mutant (SGK1‐SD) significantly enhanced cell motility. The cell‐adhesion protein vinculin was effectively dephosphorylated in SGK1‐SD‐transfected cells. Treatment of the cells with phosphatase inhibitors restored vinculin phosphorylation and inhibited cell migration, indicating a significant role for vinculin phosphorylation in SGK1‐induced motility. SGK1‐SD‐enhanced cell motility was inhibited by activation of membrane androgen‐binding sites (mAR) via testosterone‐conjugates in both cell lines, whereas intracellular androgen receptor (iAR)‐silencing and flutamide treatment revealed that these effects were clearly independent of the interaction of SGK1 with the classical androgen receptors (iAR). More importantly, mAR activation restored vinculin phosphorylation in SGK1‐SD‐transfected cells, whereas silencing of vinculin fully reversed the mAR‐induced inhibition of the migratory capacity, implying that this protein is directly involved in cell motility regulation by SGK1 and mAR. This study indicates for the first time that SGK1 regulates cell migration via vinculin dephosphorylation, a mechanism that is controlled by mAR function.

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