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Title: Minimally disruptive optical control of protein tyrosine phosphatase 1B

Abstract

Protein tyrosine phosphatases regulate a myriad of essential subcellular signaling events, yet they remain difficult to study in their native biophysical context. Here we develop a minimally disruptive optical approach to control protein tyrosine phosphatase 1B (PTP1B)—an important regulator of receptor tyrosine kinases and a therapeutic target for the treatment of diabetes, obesity, and cancer—and we use that approach to probe the intracellular function of this enzyme. Our conservative architecture for photocontrol, which consists of a protein-based light switch fused to an allosteric regulatory element, preserves the native structure, activity, and subcellular localization of PTP1B, affords changes in activity that match those elicited by post-translational modifications inside the cell, and permits experimental analyses of the molecular basis of optical modulation. Findings indicate, most strikingly, that small changes in the activity of PTP1B can cause large shifts in the phosphorylation states of its regulatory targets.

Authors:
 [1];  [2];  [2]; ORCiD logo [1]
  1. Univ. of Colorado, Boulder, CO (United States)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Science Foundation (NSF); National Institutes of Health (NIH)
OSTI Identifier:
1615301
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Hongdusit, Akarawin, Zwart, Peter H., Sankaran, Banumathi, and Fox, Jerome M.. Minimally disruptive optical control of protein tyrosine phosphatase 1B. United States: N. p., 2020. Web. https://doi.org/10.1038/s41467-020-14567-8.
Hongdusit, Akarawin, Zwart, Peter H., Sankaran, Banumathi, & Fox, Jerome M.. Minimally disruptive optical control of protein tyrosine phosphatase 1B. United States. https://doi.org/10.1038/s41467-020-14567-8
Hongdusit, Akarawin, Zwart, Peter H., Sankaran, Banumathi, and Fox, Jerome M.. Fri . "Minimally disruptive optical control of protein tyrosine phosphatase 1B". United States. https://doi.org/10.1038/s41467-020-14567-8. https://www.osti.gov/servlets/purl/1615301.
@article{osti_1615301,
title = {Minimally disruptive optical control of protein tyrosine phosphatase 1B},
author = {Hongdusit, Akarawin and Zwart, Peter H. and Sankaran, Banumathi and Fox, Jerome M.},
abstractNote = {Protein tyrosine phosphatases regulate a myriad of essential subcellular signaling events, yet they remain difficult to study in their native biophysical context. Here we develop a minimally disruptive optical approach to control protein tyrosine phosphatase 1B (PTP1B)—an important regulator of receptor tyrosine kinases and a therapeutic target for the treatment of diabetes, obesity, and cancer—and we use that approach to probe the intracellular function of this enzyme. Our conservative architecture for photocontrol, which consists of a protein-based light switch fused to an allosteric regulatory element, preserves the native structure, activity, and subcellular localization of PTP1B, affords changes in activity that match those elicited by post-translational modifications inside the cell, and permits experimental analyses of the molecular basis of optical modulation. Findings indicate, most strikingly, that small changes in the activity of PTP1B can cause large shifts in the phosphorylation states of its regulatory targets.},
doi = {10.1038/s41467-020-14567-8},
journal = {Nature Communications},
number = 1,
volume = 11,
place = {United States},
year = {2020},
month = {2}
}

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