A novel domain of caveolin-2 that controls nuclear targeting: regulation of insulin-specific ERK activation and nuclear translocation by caveolin-2.
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.
Kwon
Hayeong
H
Department of Biochemistry, Division of Applied Life Science, PMBBRC, Gyeongsang National University, Jinju, Korea.
Jeong
Kyuho
K
Hwang
Eun Mi
EM
Park
Jae-Yong
JY
Pak
Yunbae
Y
D000818:Animals; D019556:COS Cells; D051243:Caveolin 2 / Q000737:chemistry* / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology*; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D034882:Lamins / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
D051243:Caveolin 2; D007328:Insulin; D034882:Lamins; D050505:Mutant Proteins; D021382:Protein Sorting Signals; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D048049:Extracellular Signal-Regulated MAP Kinases
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