N-myristoylation regulates insulin-induced phosphorylation and ubiquitination of Caveolin-2 for insulin signaling
- Kwon, Hayeong; Choi, Moonjeong; Ahn, Yujin; Pak, Yunbae
- Issue Date
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- N-myristoylation; Caveolin-2; Phosphorylation; Ubiquitination; Insulin receptor; Protein-tyrosine phosphatase 1B
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.532, no.4, pp.535 - 540
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Start Page
- End Page
- N-myristoylation is a ubiquitous protein lipidation in eukaryotes, but regulatory roles for myristoylation on proteins still remain to be explored. Here, we show that N-myristoylation of Caveolin-2 (Cav-2) controls insulin signaling. Alternative translation initiation (ATI)-yielded truncated form of non-N-myristoylable Cav-2 beta and various conditional Cav-2 mutants were compared to full-length form of N-myristoylable Cav-2 alpha. Insulin induced insulin receptor (IR) tyrosine kinase-catalyzed Tyr-19 phosphorylation of N-myristoylable M14A Cav-2 and triggered activation of IR signaling cascade. In contrast, insulin induced ubiquitination of non-N-myristoylable MIA and G2A Cav-2 to facilitate protein-tyrosine phosphatase 1B interaction with IR which desensitized IR signaling through internalization. Metabolic labeling and click chemistry showed palmitoylation of M14A but not MIA and G2A Cav-2. Insulin did not induce phosphorylation of MIA and G2A Cav-2 and Cav-2 beta. Like Cav-2 alpha, G2A Cav-2 and Cav-2 beta formed large homo-oligomers localized in lipid rafts. These findings show Cav-2 N-myristoylation plays a crucial role to coordinate its phosphorylation, palmitoylation, and ubiquitination to control insulin signaling. (C) 2020 Elsevier Inc. All rights reserved.
- Files in This Item
- There are no files associated with this item.
- Appears in
- ETC > Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.