A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction]
Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang
The American Society for Biochemistry and Molecular Biology (ASBMB)
Published 2018
The American Society for Biochemistry and Molecular Biology (ASBMB)
Published 2018
| Publication Date: |
2018-02-08
|
|---|---|
| Publisher: |
The American Society for Biochemistry and Molecular Biology (ASBMB)
|
| Print ISSN: |
0021-9258
|
| Electronic ISSN: |
1083-351X
|
| Topics: |
Biology
Chemistry and Pharmacology
|
| Published by: |
| _version_ | 1836398783969099779 |
|---|---|
| autor | Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang |
| beschreibung | A diverse group of cell-surface receptors, including many G protein-coupled receptors and receptor tyrosine kinases, activate phospholipase C (PLC) isozymes to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and 1,4,5-inositol trisphosphate. Consequently, PLCs control various cellular processes, and their aberrant regulation contributes to many diseases, including cancer, atherosclerosis, and rheumatoid arthritis. Despite the widespread importance of PLCs in human biology and disease, it has been impossible to directly monitor the real-time activation of these enzymes at membranes. To overcome this limitation, here we describe XY-69, a fluorogenic reporter that preferentially partitions into membranes and provides a selective tool for measuring the real-time activity of PLCs as either purified enzymes or in cellular lysates. Indeed, XY-69 faithfully reported the membrane-dependent activation of PLC-β3 by Gαq. Therefore, XY-69 can replace radioactive phosphatidylinositol 4,5-bisphosphate used in conventional PLC assays and will enable high-throughput screens to identify both orthosteric and allosteric PLC inhibitors. In the future, cell-permeable variants of XY-69 represent promising candidates for reporting the activation of PLCs in live cells with high spatiotemporal resolution. |
| citation_standardnr | 6158889 |
| datenlieferant | ipn_articles |
| feed_id | 43 |
| feed_publisher | The American Society for Biochemistry and Molecular Biology (ASBMB) |
| feed_publisher_url | http://www.asbmb.org/ |
| insertion_date | 2018-02-08 |
| journaleissn | 1083-351X |
| journalissn | 0021-9258 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Society for Biochemistry and Molecular Biology (ASBMB) |
| quelle | Journal of Biological Chemistry |
| relation | http://feedproxy.google.com/~r/jbc/SUcv/~3/sPPPm--Rp-I/1728.short |
| search_space | articles |
| shingle_author_1 | Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang |
| shingle_author_2 | Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang |
| shingle_author_3 | Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang |
| shingle_author_4 | Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang |
| shingle_catch_all_1 | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] A diverse group of cell-surface receptors, including many G protein-coupled receptors and receptor tyrosine kinases, activate phospholipase C (PLC) isozymes to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and 1,4,5-inositol trisphosphate. Consequently, PLCs control various cellular processes, and their aberrant regulation contributes to many diseases, including cancer, atherosclerosis, and rheumatoid arthritis. Despite the widespread importance of PLCs in human biology and disease, it has been impossible to directly monitor the real-time activation of these enzymes at membranes. To overcome this limitation, here we describe XY-69, a fluorogenic reporter that preferentially partitions into membranes and provides a selective tool for measuring the real-time activity of PLCs as either purified enzymes or in cellular lysates. Indeed, XY-69 faithfully reported the membrane-dependent activation of PLC-β3 by Gαq. Therefore, XY-69 can replace radioactive phosphatidylinositol 4,5-bisphosphate used in conventional PLC assays and will enable high-throughput screens to identify both orthosteric and allosteric PLC inhibitors. In the future, cell-permeable variants of XY-69 represent promising candidates for reporting the activation of PLCs in live cells with high spatiotemporal resolution. Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang The American Society for Biochemistry and Molecular Biology (ASBMB) 0021-9258 00219258 1083-351X 1083351X |
| shingle_catch_all_2 | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] A diverse group of cell-surface receptors, including many G protein-coupled receptors and receptor tyrosine kinases, activate phospholipase C (PLC) isozymes to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and 1,4,5-inositol trisphosphate. Consequently, PLCs control various cellular processes, and their aberrant regulation contributes to many diseases, including cancer, atherosclerosis, and rheumatoid arthritis. Despite the widespread importance of PLCs in human biology and disease, it has been impossible to directly monitor the real-time activation of these enzymes at membranes. To overcome this limitation, here we describe XY-69, a fluorogenic reporter that preferentially partitions into membranes and provides a selective tool for measuring the real-time activity of PLCs as either purified enzymes or in cellular lysates. Indeed, XY-69 faithfully reported the membrane-dependent activation of PLC-β3 by Gαq. Therefore, XY-69 can replace radioactive phosphatidylinositol 4,5-bisphosphate used in conventional PLC assays and will enable high-throughput screens to identify both orthosteric and allosteric PLC inhibitors. In the future, cell-permeable variants of XY-69 represent promising candidates for reporting the activation of PLCs in live cells with high spatiotemporal resolution. Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang The American Society for Biochemistry and Molecular Biology (ASBMB) 0021-9258 00219258 1083-351X 1083351X |
| shingle_catch_all_3 | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] A diverse group of cell-surface receptors, including many G protein-coupled receptors and receptor tyrosine kinases, activate phospholipase C (PLC) isozymes to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and 1,4,5-inositol trisphosphate. Consequently, PLCs control various cellular processes, and their aberrant regulation contributes to many diseases, including cancer, atherosclerosis, and rheumatoid arthritis. Despite the widespread importance of PLCs in human biology and disease, it has been impossible to directly monitor the real-time activation of these enzymes at membranes. To overcome this limitation, here we describe XY-69, a fluorogenic reporter that preferentially partitions into membranes and provides a selective tool for measuring the real-time activity of PLCs as either purified enzymes or in cellular lysates. Indeed, XY-69 faithfully reported the membrane-dependent activation of PLC-β3 by Gαq. Therefore, XY-69 can replace radioactive phosphatidylinositol 4,5-bisphosphate used in conventional PLC assays and will enable high-throughput screens to identify both orthosteric and allosteric PLC inhibitors. In the future, cell-permeable variants of XY-69 represent promising candidates for reporting the activation of PLCs in live cells with high spatiotemporal resolution. Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang The American Society for Biochemistry and Molecular Biology (ASBMB) 0021-9258 00219258 1083-351X 1083351X |
| shingle_catch_all_4 | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] A diverse group of cell-surface receptors, including many G protein-coupled receptors and receptor tyrosine kinases, activate phospholipase C (PLC) isozymes to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and 1,4,5-inositol trisphosphate. Consequently, PLCs control various cellular processes, and their aberrant regulation contributes to many diseases, including cancer, atherosclerosis, and rheumatoid arthritis. Despite the widespread importance of PLCs in human biology and disease, it has been impossible to directly monitor the real-time activation of these enzymes at membranes. To overcome this limitation, here we describe XY-69, a fluorogenic reporter that preferentially partitions into membranes and provides a selective tool for measuring the real-time activity of PLCs as either purified enzymes or in cellular lysates. Indeed, XY-69 faithfully reported the membrane-dependent activation of PLC-β3 by Gαq. Therefore, XY-69 can replace radioactive phosphatidylinositol 4,5-bisphosphate used in conventional PLC assays and will enable high-throughput screens to identify both orthosteric and allosteric PLC inhibitors. In the future, cell-permeable variants of XY-69 represent promising candidates for reporting the activation of PLCs in live cells with high spatiotemporal resolution. Weigang Huang, Xiaoyang Wang, Stuart Endo-Streeter, Matthew Barrett, Jarod Waybright, Christian Wohlfeld, Nicole Hajicek, T. Kendall Harden, John Sondek, Qisheng Zhang The American Society for Biochemistry and Molecular Biology (ASBMB) 0021-9258 00219258 1083-351X 1083351X |
| shingle_title_1 | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] |
| shingle_title_2 | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] |
| shingle_title_3 | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] |
| shingle_title_4 | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] |
| timestamp | 2025-06-30T23:32:34.865Z |
| titel | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] |
| titel_suche | A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes [Signal Transduction] |
| topic | W V |
| uid | ipn_articles_6158889 |