Downregulation of protein tyrosine phosphatase PTP-BL represses adipogenesis.
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.
IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, France.
Murielle
M
Glondu-Lassis
Mathilde
M
Dromard
Carine
C
Chavey
Carole
C
Puech
Lluis
L
Fajas
Wiljan
W
Hendriks
Gilles
G
Freiss
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000201:enzymology; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002999:Clone Cells; D015536:Down-Regulation / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D051379:Mice; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13