IGFBP-5 regulates muscle cell differentiation by binding to IGF-II and switching on the IGF-II auto-regulation loop

Hongxia Ren, Ping Yin, Cunming Duan

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

IGF-II stimulates both mitogenesis and myogenesis through its binding and activation of the IGF-I receptor (IGF-IR). How this growth factor pathway promotes these two opposite cellular responses is not well understood. We investigate whether local IGF binding protein-5 (IGFBP-5) promotes the myogenic action of IGF-II. IGFBP-5 is induced before the elevation of IGF-II expression during myogenesis. Knockdown of IGFBP-5 impairs myogenesis and suppresses IGF-II gene expression. IGF-II up-regulates its own gene expression via the PI3K-Akt signaling pathway. Adding IGF-II or constitutively activating Akt rescues the IGFBP-5 knockdown-caused defects. However, an IGF analogue that binds to the IGF-IR but not IGFBP has only a limited effect. When added with low concentrations of IGF-II, IGFBP-5 restores IGF-II expression and myogenic differentiation, whereas an IGF binding-deficient IGFBP-5 mutant has no effect. These findings suggest that IGFBP-5 promotes muscle cell differentiation by binding to and switching on the IGF-II auto-regulation loop.

Original languageEnglish (US)
Pages (from-to)979-991
Number of pages13
JournalJournal of Cell Biology
Volume182
Issue number5
DOIs
StatePublished - Sep 8 2008
Externally publishedYes

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Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor II
Muscle Cells
Cell Differentiation
Muscle Development
IGF Type 1 Receptor
Gene Expression
Insulin-Like Growth Factor Binding Proteins
Phosphatidylinositol 3-Kinases
Intercellular Signaling Peptides and Proteins
Up-Regulation

ASJC Scopus subject areas

  • Cell Biology

Cite this

IGFBP-5 regulates muscle cell differentiation by binding to IGF-II and switching on the IGF-II auto-regulation loop. / Ren, Hongxia; Yin, Ping; Duan, Cunming.

In: Journal of Cell Biology, Vol. 182, No. 5, 08.09.2008, p. 979-991.

Research output: Contribution to journalArticle

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AB - IGF-II stimulates both mitogenesis and myogenesis through its binding and activation of the IGF-I receptor (IGF-IR). How this growth factor pathway promotes these two opposite cellular responses is not well understood. We investigate whether local IGF binding protein-5 (IGFBP-5) promotes the myogenic action of IGF-II. IGFBP-5 is induced before the elevation of IGF-II expression during myogenesis. Knockdown of IGFBP-5 impairs myogenesis and suppresses IGF-II gene expression. IGF-II up-regulates its own gene expression via the PI3K-Akt signaling pathway. Adding IGF-II or constitutively activating Akt rescues the IGFBP-5 knockdown-caused defects. However, an IGF analogue that binds to the IGF-IR but not IGFBP has only a limited effect. When added with low concentrations of IGF-II, IGFBP-5 restores IGF-II expression and myogenic differentiation, whereas an IGF binding-deficient IGFBP-5 mutant has no effect. These findings suggest that IGFBP-5 promotes muscle cell differentiation by binding to and switching on the IGF-II auto-regulation loop.

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