Downregulation of protein tyrosine phosphatase PTP-BL represses adipogenesis.

Détails

ID Serval
serval:BIB_955F92E93F52
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Downregulation of protein tyrosine phosphatase PTP-BL represses adipogenesis.
Périodique
International Journal of Biochemistry and Cell Biology
Auteur(s)
Glondu-Lassis M., Dromard M., Chavey C., Puech C., Fajas L., Hendriks W., Freiss G.
ISSN
1878-5875 (Electronic)
ISSN-L
1357-2725
Statut éditorial
Publié
Date de publication
2009
Volume
41
Numéro
11
Pages
2173-2180
Langue
anglais
Résumé
The insulin/insulin-like growth factor 1 (IGF-1) signaling pathway is a major regulator of adipose tissue growth and differentiation. We recently demonstrated that human protein tyrosine phosphatase (PTP) L1, a large cytoplasmic phosphatase also known as PTP-BAS/PTPN13/PTP-1E, is a negative regulator of IGF-1R/IRS-1/Akt pathway in breast cancer cells. This triggered us to investigate the potential role of PTPL1 in adipogenesis. To evaluate the implication of PTP-BL, the mouse orthologue of PTPL1, in adipose tissue biology, we analyzed PTP-BL mRNA expression in adipose tissue in vivo and during proliferation and differentiation of 3T3-L1 pre-adipocytes. To elucidate the role of PTP-BL and of its catalytic activity during adipogenesis we use siRNA techniques in 3T3-L1 pre-adipocytes, and mouse embryonic fibroblasts that lack wildtype PTP-BL and instead express a variant without the PTP domain (Delta P/Delta P MEFs). Here we show that PTP-BL is strongly expressed in white adipose tissue and that PTP-BL transcript and protein levels increase during proliferation and differentiation of 3T3-L1 pre-adipocytes. Strikingly, knockdown of PTP-BL expression in 3T3-L1 adipocytes caused a dramatic decrease in adipogenic gene expression levels (PPAR gamma, aP2) and lipid accumulation but did not interfere with the insulin/Akt pathway. Delta P/Delta P MEFs differentiate into the adipogenic lineage as efficiently as wildtype MEFs. However, when expression of either PTP-BL or PTP-BL Delta P was inhibited a dramatic reduction in the number of MEF-derived adipocytes was observed. These findings demonstrate a key role for PTP-BL in 3T3-L1 and MEF-derived adipocyte differentiation that is independent of its enzymatic activity.
Mots-clé
3T3-L1 Cells, Adipocytes/cytology, Adipocytes/enzymology, Adipogenesis/genetics, Animals, Cell Differentiation, Cell Proliferation, Clone Cells, Down-Regulation/genetics, Gene Expression Regulation, Enzymologic, Gene Knockdown Techniques, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 13/antagonists & inhibitors, Protein Tyrosine Phosphatase, Non-Receptor Type 13/genetics
Pubmed
Web of science
Création de la notice
07/03/2013 17:00
Dernière modification de la notice
03/03/2018 19:40
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