Direct integrin binding to insulin-like growth factor-2 through the C-domain is required for insulin-like growth factor receptor type 1 (IGF1R) signaling

Dora Maria Cedano Prieto, Yushen Cheng, Chih Chieh Chang, Jessica Yu, Yoko K. Takada, Yoshikazu Takada

研究成果: 雜誌貢獻文章

3 引文 (Scopus)

摘要

We have reported that integrins crosstalk with growth factors through direct binding to growth factors (e.g., fibroblast growth factor-1, insulin-like growth factor 1 (IGF1), neuregulin-1, fractalkine) and subsequent ternary complex formation with cognate receptor [e.g., integrin/ IGF1/IGF1 receptor (IGF1R)]. IGF1 and IGF2 are overexpressed in cancer and major therapeutic targets. We previously reported that IGF1 binds to integrins ανβ3 and α6β4, and the R36E/R37E mutant in the C-domain of IGF1 is defective integrin binding and signaling functions of IGF1, and acts as an antagonist of IGF1R. We studied if integrins play a role in the signaling functions of IGF2, another member of the IGF family. Here we describe that IGF2 specifically binds to integrins ανβ3 and α6β4, and induced proliferation of CHO cells (IGF1R+) that express ανβ3 or α6β4 (β3- or α6β4-CHO cells). Arg residues to Glu at positions 24, 34, 37 and/or 38 in or close to the C-domain of IGF2 play a critical role in binding to integrins and signaling functions. The R24E/R37E/R38E, R34E/R37E/R38E, and R24E/R34E/R37E/R38E mutants were defective in integrin binding and IGF2 signaling. These mutants suppressed proliferation induced by WT IGF2, suggesting that they are dominant-negative antagonists of IGF1R. These results suggest that IGF2 also requires integrin binding for signaling functions, and the IGF2 mutants that cannot bind to integrins act as antagonists of IGF1R. The present study defines the role of the C-domain in integrin binding and signaling.

原文英語
文章編號e0184285
期刊PLoS One
12
發行號9
DOIs
出版狀態已發佈 - 九月 1 2017

指紋

IGF Type 1 Receptor
integrins
somatomedins
Somatomedins
Integrins
receptors
antagonists
mutants
CHO Cells
growth factors
Intercellular Signaling Peptides and Proteins
fibroblast growth factor 1
Chemokine CX3CL1
Neuregulin-1
Somatomedin Receptors
Fibroblast Growth Factor 1
Crosstalk
cell proliferation

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

引用此文

Direct integrin binding to insulin-like growth factor-2 through the C-domain is required for insulin-like growth factor receptor type 1 (IGF1R) signaling. / Prieto, Dora Maria Cedano; Cheng, Yushen; Chang, Chih Chieh; Yu, Jessica; Takada, Yoko K.; Takada, Yoshikazu.

於: PLoS One, 卷 12, 編號 9, e0184285, 01.09.2017.

研究成果: 雜誌貢獻文章

Prieto, Dora Maria Cedano ; Cheng, Yushen ; Chang, Chih Chieh ; Yu, Jessica ; Takada, Yoko K. ; Takada, Yoshikazu. / Direct integrin binding to insulin-like growth factor-2 through the C-domain is required for insulin-like growth factor receptor type 1 (IGF1R) signaling. 於: PLoS One. 2017 ; 卷 12, 編號 9.
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AU - Takada, Yoko K.

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