Abstract
Herein, we report that insulin-activated extracellular signal-regulated kinase (ERK) is translocated to the nuclear envelope by caveolin-2 (cav-2) and associates with lamin A/C in the inner nuclear membrane in response to insulin. We identified that the Ser154-Val155-Ser156 domain on the C-terminal of cav-2 is essential for insulin-induced phosphorylation and nuclear targeting of ERK and cav-2. In human embryonic kidney 293T cells, ERK was not activated and translocated to the nucleus by insulin in comparison to insulin-like growth factor-1 (IGF-1). However, insulin-stimulated activation of ERK was induced by exogenous addition of cav-2. The activated ERK associated and translocated with the cav-2 to the nucleus. In turn, cav-2 promoted phospho-ERK interaction with lamin A/C in the inner nuclear membrane. In contrast, ERK, but not cav-2, was phosphorylated and translocated to the nucleus by IGF-1. The nuclear targeted phospho-ERK failed to localize in the nuclear envelope in response to IGF-1. Together, our data demonstrate that translocation of phospho-ERK to the nuclear envelope is mediated by Ser154-Val155-Ser156 domain of cav-2 and this event is an insulin-specific action.
Original language | English |
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Pages (from-to) | 888-908 |
Number of pages | 21 |
Journal | Journal of Cellular and Molecular Medicine |
Volume | 15 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2011 Apr |
Externally published | Yes |
Keywords
- Caveolin-2
- IGF-1
- Insulin
- Lamin A/C
- Nuclear translocation
- Phospho-ERK
ASJC Scopus subject areas
- Molecular Medicine
- Cell Biology