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

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.

• Authors: Donghwan Jang, Hayeong Kwon, Kyuho Jeong, Jaewoong Lee, Yunbae Pak
• Journal: Journal of cell science (J Cell Sci) Vol. 128 Issue 11 Pg. 2179-90 (Jun 01 2015) ISSN: 1477-9137 [Electronic] England
• PMID: 25908865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015. Published by The Company of Biologists Ltd.

Chemical References

• Membrane Proteins
• flotillins
• Insulin-Like Growth Factor I
• Protein-Tyrosine Kinases
• Receptor, IGF Type 1
• Proto-Oncogene Proteins c-akt

Topics

• Cell Line, Tumor
• Cell Proliferation (physiology)
• Endoplasmic Reticulum (metabolism)
• HEK293 Cells
• HeLa Cells
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Lipoylation (physiology)
• MAP Kinase Signaling System (physiology)
• Membrane Proteins (metabolism)
• Protein-Tyrosine Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, IGF Type 1 (metabolism)
• Signal Transduction (physiology)