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Downregulation of protein tyrosine phosphatase PTP-BL represses adipogenesis.

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00422382
Contributor : Yves Le Ster <>
Submitted on : Tuesday, October 6, 2009 - 4:38:37 PM
Last modification on : Sunday, December 15, 2019 - 10:20:04 PM
Long-term archiving on: : Wednesday, June 16, 2010 - 12:24:05 AM

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Murielle Glondu-Lassis, Mathilde Dromard, Carine Chavey, Carole Puech, Lluis Fajas, et al.. Downregulation of protein tyrosine phosphatase PTP-BL represses adipogenesis.. International Journal of Biochemistry and Cell Biology, Elsevier, 2009, 41 (11), pp.2173-80. ⟨10.1016/j.biocel.2009.04.004⟩. ⟨inserm-00422382⟩

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