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Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor gamma messenger ribonucleic acid levels.
- Source :
-
Molecular endocrinology (Baltimore, Md.) [Mol Endocrinol] 2007 May; Vol. 21 (5), pp. 1120-31. Date of Electronic Publication: 2007 Feb 20. - Publication Year :
- 2007
-
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 gamma (PPARgamma) 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 PPARgamma in 3T3-L1 cells, whereas PPARgamma levels were reduced in SH2-B-deficient MEFs in response to insulin. SH2-B-mediated up-regulation of PPARgamma 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 PPARgamma transcription, were up-regulated by SH2-B overexpression, but reduced in SH2-B-deficient 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-PPARgamma pathway.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Animals
Base Sequence
Cell Culture Techniques
Cell Differentiation
DNA Primers
Mice
Mice, Knockout
Reverse Transcriptase Polymerase Chain Reaction
src Homology Domains
Adaptor Proteins, Signal Transducing metabolism
Adipocytes cytology
PPAR gamma genetics
Proto-Oncogene Proteins c-akt metabolism
RNA, Messenger genetics
Receptor Protein-Tyrosine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0888-8809
- Volume :
- 21
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular endocrinology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 17312274
- Full Text :
- https://doi.org/10.1210/me.2006-0413