期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 11, 页码 2179-2190出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.169409
关键词
Flotillin-1; Palmitoylation; IGF-1 receptor; Flotillin-2
类别
资金
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [2011-0014898]
- Ministry of Education [2012R1A1A2041550]
- Next-Generation BioGreen 21 Program (SSAC) from the Rural Development Administration of Korea [PJ01137901]
- BK21 Plus Program
- NRF [2013H1A2A1034489]
- National Research Foundation of Korea [2013H1A2A1034489, 2011-0014898] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Here, we explored flotillin-1-mediated regulation of insulin-like growth factor-1 (IGF-1) signaling. Flotillin-1-deficient cells exhibited a reduction in the activation of IGF-1 receptor (IGF-1R), ERK1/2 and Akt pathways, and the transcriptional activation of Elk-1 and the proliferation in response to IGF-1 were reduced in these cells. We found that IGF-1-independent flotillin-1 palmitoylation at Cys34 in the endoplasmic reticulum (ER) was required for the ER exit and the plasma membrane localization of flotillin-1 and IGF-1R. IGF-1-dependent depalmitoylation and repalmitoylation of flotillin-1 sustained tyrosine kinase activation of the plasma-membrane-targeted IGF-1R. Dysfunction and blocking the turnover of flotillin-1 palmitoylation abrogated cancer cell proliferation after IGF-1R signaling activation. Our data show that flotillin-1 palmitoylation is a new mechanism by which the intracellular localization and activation of IGF-1R are controlled.
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