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J Cell Sci. 2015 Jun 1;128(11):2179-90. doi: 10.1242/jcs.169409. Epub 2015 Apr 23.

Essential role of flotillin-1 palmitoylation in the intracellular localization and signaling function of IGF-1 receptor.

Author information

1
Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.
2
Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea ybpak@gnu.ac.kr.

Abstract

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.

KEYWORDS:

Flotillin-1; Flotillin-2; IGF-1 receptor; Palmitoylation

PMID:
25908865
DOI:
10.1242/jcs.169409
[Indexed for MEDLINE]
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