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PTP1B-dependent insulin receptor phosphorylation/residency in the endocytic recycling compartment of CHO-IR cells.
Biochem Pharmacol 2006; 72(10):1279-92BP

Abstract

Insulin binds to the alpha subunit of the insulin receptor (IR) on the cell surface. The insulin-IR complex is subsequently internalized and trafficked within the cell. Endocytosed receptors, devoid of insulin, recycle back to the plasma membrane through the endocytic recycling compartment (ERC). Using a high content screening system, we investigate the intracellular trafficking of the IR and its phosphorylation state, within the ERC, in response to protein tyrosine phosphatase-1B (PTP1B) inhibition. Insulin stimulates, in a time- and dose-dependent manner, the accumulation of phosphorylated IR (pY(1158,1162,1163 IR) in the ERC of CHO-IR cells. Treatment of CHO-IR cells with PTP1B-specific inhibitors or siRNA leads to dose-dependent increases in IR residency and phosphorylation within the ERC. The results also demonstrate that PTP1B redistributes within CHO-IR cells upon insulin challenge. The established system will allow for efficient screening of candidate inhibitors for the modulation of PTP1B activity.

Authors+Show Affiliations

Department of Biochemistry & Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe-Claire-Dorval, Pointe-Claire-Dorval, Quebec, Canada. wanda_cromlish@merck.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16956584

Citation

Cromlish, Wanda A., et al. "PTP1B-dependent Insulin Receptor Phosphorylation/residency in the Endocytic Recycling Compartment of CHO-IR Cells." Biochemical Pharmacology, vol. 72, no. 10, 2006, pp. 1279-92.
Cromlish WA, Tang M, Kyskan R, et al. PTP1B-dependent insulin receptor phosphorylation/residency in the endocytic recycling compartment of CHO-IR cells. Biochem Pharmacol. 2006;72(10):1279-92.
Cromlish, W. A., Tang, M., Kyskan, R., Tran, L., & Kennedy, B. P. (2006). PTP1B-dependent insulin receptor phosphorylation/residency in the endocytic recycling compartment of CHO-IR cells. Biochemical Pharmacology, 72(10), pp. 1279-92.
Cromlish WA, et al. PTP1B-dependent Insulin Receptor Phosphorylation/residency in the Endocytic Recycling Compartment of CHO-IR Cells. Biochem Pharmacol. 2006 Nov 15;72(10):1279-92. PubMed PMID: 16956584.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PTP1B-dependent insulin receptor phosphorylation/residency in the endocytic recycling compartment of CHO-IR cells. AU - Cromlish,Wanda A, AU - Tang,Man, AU - Kyskan,Robert, AU - Tran,Linda, AU - Kennedy,Brian P, Y1 - 2006/09/07/ PY - 2006/06/15/received PY - 2006/07/31/revised PY - 2006/07/31/accepted PY - 2006/9/8/pubmed PY - 2006/12/16/medline PY - 2006/9/8/entrez SP - 1279 EP - 92 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 72 IS - 10 N2 - Insulin binds to the alpha subunit of the insulin receptor (IR) on the cell surface. The insulin-IR complex is subsequently internalized and trafficked within the cell. Endocytosed receptors, devoid of insulin, recycle back to the plasma membrane through the endocytic recycling compartment (ERC). Using a high content screening system, we investigate the intracellular trafficking of the IR and its phosphorylation state, within the ERC, in response to protein tyrosine phosphatase-1B (PTP1B) inhibition. Insulin stimulates, in a time- and dose-dependent manner, the accumulation of phosphorylated IR (pY(1158,1162,1163 IR) in the ERC of CHO-IR cells. Treatment of CHO-IR cells with PTP1B-specific inhibitors or siRNA leads to dose-dependent increases in IR residency and phosphorylation within the ERC. The results also demonstrate that PTP1B redistributes within CHO-IR cells upon insulin challenge. The established system will allow for efficient screening of candidate inhibitors for the modulation of PTP1B activity. SN - 0006-2952 UR - https://www.unboundmedicine.com/medline/citation/16956584/PTP1B_dependent_insulin_receptor_phosphorylation/residency_in_the_endocytic_recycling_compartment_of_CHO_IR_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(06)00492-8 DB - PRIME DP - Unbound Medicine ER -