Noninvasive in Vivo Imaging of Protein Kinase a Activity

Protein kinases play pivotal roles in almost all cellular signaling pathways, and modulation of their activity is desirable in both disease and studies of function. Information on the activity of kinases in vivo is scarce owing to a lack of appropriate methods. To obtain such information, we produce...

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Main Authors: Jan Øivind Moskaug, Harald Carlsen, Rune Blomhoff
Format: Article
Language:English
Published: SAGE Publishing 2008-01-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2008.0005
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author Jan Øivind Moskaug
Harald Carlsen
Rune Blomhoff
author_facet Jan Øivind Moskaug
Harald Carlsen
Rune Blomhoff
author_sort Jan Øivind Moskaug
collection DOAJ
description Protein kinases play pivotal roles in almost all cellular signaling pathways, and modulation of their activity is desirable in both disease and studies of function. Information on the activity of kinases in vivo is scarce owing to a lack of appropriate methods. To obtain such information, we produced mice in which protein kinase A (PKA) activity can be monitored noninvasively in vivo. The model uses luciferase, which has been mutated to contain a target sequence of PKA, thus making luminescence from the enzyme dependent on its state of phosphorylation. The PKA-sensitive luciferase, termed luciferase PKA , was incorporated into the mouse genome, and transgenic animals exhibited a rapid β-adrenergic response, that is, reduced luminescence, in various organs, including the pancreas, muscle, liver, and fat, after isoproterenol injection. This study shows that luciferase can be used for in vivo measurements of kinase activity, suggesting that different kinase target sequences in luciferase can monitor kinase activity modulation.
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spelling doaj-art-f3f785db90794e4f8872ffff450951172025-01-02T22:41:16ZengSAGE PublishingMolecular Imaging1536-01212008-01-01710.2310/7290.2008.000510.2310_7290.2008.0005Noninvasive in Vivo Imaging of Protein Kinase a ActivityJan Øivind MoskaugHarald CarlsenRune BlomhoffProtein kinases play pivotal roles in almost all cellular signaling pathways, and modulation of their activity is desirable in both disease and studies of function. Information on the activity of kinases in vivo is scarce owing to a lack of appropriate methods. To obtain such information, we produced mice in which protein kinase A (PKA) activity can be monitored noninvasively in vivo. The model uses luciferase, which has been mutated to contain a target sequence of PKA, thus making luminescence from the enzyme dependent on its state of phosphorylation. The PKA-sensitive luciferase, termed luciferase PKA , was incorporated into the mouse genome, and transgenic animals exhibited a rapid β-adrenergic response, that is, reduced luminescence, in various organs, including the pancreas, muscle, liver, and fat, after isoproterenol injection. This study shows that luciferase can be used for in vivo measurements of kinase activity, suggesting that different kinase target sequences in luciferase can monitor kinase activity modulation.https://doi.org/10.2310/7290.2008.0005
spellingShingle Jan Øivind Moskaug
Harald Carlsen
Rune Blomhoff
Noninvasive in Vivo Imaging of Protein Kinase a Activity
Molecular Imaging
title Noninvasive in Vivo Imaging of Protein Kinase a Activity
title_full Noninvasive in Vivo Imaging of Protein Kinase a Activity
title_fullStr Noninvasive in Vivo Imaging of Protein Kinase a Activity
title_full_unstemmed Noninvasive in Vivo Imaging of Protein Kinase a Activity
title_short Noninvasive in Vivo Imaging of Protein Kinase a Activity
title_sort noninvasive in vivo imaging of protein kinase a activity
url https://doi.org/10.2310/7290.2008.0005
work_keys_str_mv AT janøivindmoskaug noninvasiveinvivoimagingofproteinkinaseaactivity
AT haraldcarlsen noninvasiveinvivoimagingofproteinkinaseaactivity
AT runeblomhoff noninvasiveinvivoimagingofproteinkinaseaactivity