TY - JOUR
T1 - A novel domain of caveolin-2 that controls nuclear targeting
T2 - Regulation of insulin-specific ERK activation and nuclear translocation by caveolin-2
AU - Kwon, Hayeong
AU - Jeong, Kyuho
AU - Hwang, Eun Mi
AU - Park, Jae Yong
AU - Pak, Yunbae
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
KW - Caveolin-2
KW - IGF-1
KW - Insulin
KW - Lamin A/C
KW - Nuclear translocation
KW - Phospho-ERK
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U2 - 10.1111/j.1582-4934.2010.01079.x
DO - 10.1111/j.1582-4934.2010.01079.x
M3 - Article
C2 - 20455999
AN - SCOPUS:79954995335
VL - 15
SP - 888
EP - 908
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
SN - 1582-1838
IS - 4
ER -