Open AccessA novel domain of caveolin‐2 that controls nuclear targeting: regulation of insulin‐specific ERK activation and nuclear translocation by caveolin‐2
Author(s) -
Kwon Hayeong,
Jeong Kyuho,
Hwang Eun Mi,
Park JaeYong,
Pak Yunbae
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01079.x
Subject(s) - caveolin 1 , mapk/erk pathway , caveolin , nuclear localization sequence , chromosomal translocation , microbiology and biotechnology , insulin , insulin receptor , caveolin 3 , chemistry , biology , signal transduction , endocrinology , caveolae , nucleus , biochemistry , insulin resistance , gene
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 Ser 154 –Val 155 –Ser 156 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 Ser 154 –Val 155 –Ser 156 domain of cav‐2 and this event is an insulin‐specific action.