Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor γ messenger ribonucleic acid levels

Daigo Yoshiga, Naoichi Sato, Takehiro Torisu, Hiroyuki Mori, Ryoko Yoshida, Seiji Nakamura, Giichi Takaesu, Takashi Kobayashi, Akihiko Yoshimura

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Adipocyte differentiation is regulated by insulin and IGF-I, which transmit signals by activating their receptor tyrosine kinase. SH2-B is an adaptor protein containing pleckstrin homology and Src homology 2 (SH2) domains that have been implicated in insulin and IGF-I receptor signaling. In this study, we found a strong link between SH2-B levels and adipogenesis. The fat mass and expression of adipogenic genes including peroxisome proliferator-activated receptor γ (PPARγ) were reduced in white adipose tissue of SH2-B-/- mice. Reduced adipocyte differentiation of SH2-B-deficient mouse embryonic fibroblasts (MEFs) was observed in response to insulin and dexamethasone, whereas retroviral SH2-B overexpression enhanced differentiation of 3T3-L1 preadipocytes to adipocytes. SH2-B overexpression enhanced mRNA level of PPARγ in 3T3-L1 cells, whereas PPARγ levels were reduced in SH2-B-deficient MEFs in response to insulin. SH2-B-mediated up-regulation of PPARγ mRNA was blocked by a phosphatidylinositol 3-kinase inhibitor, but not by a MAPK kinase inhibitor. Insulin-induced Akt activation and the phosphorylation of forkhead transcription factor (FKHR/Foxo1), a negative regulator of PPARγ transcription, were up-regulated by SH2-B overexpression, but reduced in SH2-B-deficeint MEFs. These data indicate that SH2-B is a key regulator of adipogenesis both in vivo and in vitro by regulating the insulin/IGF-I receptor-Akt-Foxo1-PPARγ pathway.

Original languageEnglish
Pages (from-to)1120-1131
Number of pages12
JournalMolecular Endocrinology
Volume21
Issue number5
DOIs
Publication statusPublished - 2007 May
Externally publishedYes

Fingerprint

Peroxisome Proliferator-Activated Receptors
Receptor Protein-Tyrosine Kinases
Adipocytes
RNA
Insulin
Adipogenesis
IGF Type 1 Receptor
Proteins
Fibroblasts
Phosphatidylinositol 3-Kinase
3T3-L1 Cells
Forkhead Transcription Factors
White Adipose Tissue
Messenger RNA
src Homology Domains
Mitogen-Activated Protein Kinase Kinases
Insulin-Like Growth Factor I
Dexamethasone
Up-Regulation
Fats

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor γ messenger ribonucleic acid levels. / Yoshiga, Daigo; Sato, Naoichi; Torisu, Takehiro; Mori, Hiroyuki; Yoshida, Ryoko; Nakamura, Seiji; Takaesu, Giichi; Kobayashi, Takashi; Yoshimura, Akihiko.

In: Molecular Endocrinology, Vol. 21, No. 5, 05.2007, p. 1120-1131.

Research output: Contribution to journalArticle

Yoshiga, Daigo ; Sato, Naoichi ; Torisu, Takehiro ; Mori, Hiroyuki ; Yoshida, Ryoko ; Nakamura, Seiji ; Takaesu, Giichi ; Kobayashi, Takashi ; Yoshimura, Akihiko. / Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor γ messenger ribonucleic acid levels. In: Molecular Endocrinology. 2007 ; Vol. 21, No. 5. pp. 1120-1131.
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