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Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression.
Biochem Biophys Res Commun 2007; 363(3):626-32BB

Abstract

Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor in stimulating lipogenesis in the liver. Protein-tyrosine phosphatase 1B (PTP1B) induces SREBP-1 gene expression via protein phosphatase 2A (PP2A) activation. PTP1B is reported to be anchored on the endoplasmic reticulum (ER) via its C-terminal tail, and change in intracellular localization of PTP1B by C-terminal-truncation did not alter its inhibitory effects on insulin signaling. In this study, we investigated whether the change in intracellular localization of PTP1B could influence SREBP-1 gene expression. Overexpression of C-terminal truncated PTP1B (PTP1BdeltaCT) in rat Fao cells did not induce SREBP-1 gene expression. Furthermore, PTP1BdeltaCT failed to bind PP2A, resulting in impaired PP2A activation, whereas overexpression of wild-type PTP1B (PTP1BWT) associated with PP2A. Moreover, a membrane-targeted PTP1BDeltaCT activated PP2A with restored PP2A binding, despite the absence of its C-terminal region. Finally, overexpression of PTP1BdeltaCT into mouse primary cultured hepatocytes failed to enhance SREBP-1c mRNA, whereas membrane-targeted PTP1BdeltaCT led to enhanced SREBP-1c mRNA in hepatocytes as well as PTP1BWT. In conclusion, membrane localization of PTP1B is essential for PP2A activation, which is crucial for its enhancement of SREBP-1 gene expression.

Authors+Show Affiliations

Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17897622

Citation

Shi, K, et al. "Membrane Localization of Protein-tyrosine Phosphatase 1B Is Essential for Its Activation of Sterol Regulatory Element-binding Protein-1 Gene Expression." Biochemical and Biophysical Research Communications, vol. 363, no. 3, 2007, pp. 626-32.
Shi K, Ugi S, Shimizu S, et al. Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression. Biochem Biophys Res Commun. 2007;363(3):626-32.
Shi, K., Ugi, S., Shimizu, S., Sekine, O., Ikeda, K., Egawa, K., ... Maegawa, H. (2007). Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression. Biochemical and Biophysical Research Communications, 363(3), pp. 626-32.
Shi K, et al. Membrane Localization of Protein-tyrosine Phosphatase 1B Is Essential for Its Activation of Sterol Regulatory Element-binding Protein-1 Gene Expression. Biochem Biophys Res Commun. 2007 Nov 23;363(3):626-32. PubMed PMID: 17897622.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression. AU - Shi,K, AU - Ugi,S, AU - Shimizu,S, AU - Sekine,O, AU - Ikeda,K, AU - Egawa,K, AU - Yoshizaki,T, AU - Nagai,Y, AU - Nishio,Y, AU - Takada,T, AU - Torii,R, AU - Kimura,H, AU - Kashiwagi,A, AU - Maegawa,H, Y1 - 2007/09/17/ PY - 2007/08/10/received PY - 2007/09/10/accepted PY - 2007/9/28/pubmed PY - 2008/2/12/medline PY - 2007/9/28/entrez SP - 626 EP - 32 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 363 IS - 3 N2 - Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor in stimulating lipogenesis in the liver. Protein-tyrosine phosphatase 1B (PTP1B) induces SREBP-1 gene expression via protein phosphatase 2A (PP2A) activation. PTP1B is reported to be anchored on the endoplasmic reticulum (ER) via its C-terminal tail, and change in intracellular localization of PTP1B by C-terminal-truncation did not alter its inhibitory effects on insulin signaling. In this study, we investigated whether the change in intracellular localization of PTP1B could influence SREBP-1 gene expression. Overexpression of C-terminal truncated PTP1B (PTP1BdeltaCT) in rat Fao cells did not induce SREBP-1 gene expression. Furthermore, PTP1BdeltaCT failed to bind PP2A, resulting in impaired PP2A activation, whereas overexpression of wild-type PTP1B (PTP1BWT) associated with PP2A. Moreover, a membrane-targeted PTP1BDeltaCT activated PP2A with restored PP2A binding, despite the absence of its C-terminal region. Finally, overexpression of PTP1BdeltaCT into mouse primary cultured hepatocytes failed to enhance SREBP-1c mRNA, whereas membrane-targeted PTP1BdeltaCT led to enhanced SREBP-1c mRNA in hepatocytes as well as PTP1BWT. In conclusion, membrane localization of PTP1B is essential for PP2A activation, which is crucial for its enhancement of SREBP-1 gene expression. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/17897622/Membrane_localization_of_protein_tyrosine_phosphatase_1B_is_essential_for_its_activation_of_sterol_regulatory_element_binding_protein_1_gene_expression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(07)01974-2 DB - PRIME DP - Unbound Medicine ER -