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Exploring Obscurin and SPEG Kinase Biology
Three members of the obscurin protein family that contain tandem kinase domains with important signaling functions for cardiac and striated muscles are the giant protein obscurin, its obscurin-associated kinase splice isoform, and the striated muscle enriched protein kinase (SPEG). While there is in...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957886/ https://www.ncbi.nlm.nih.gov/pubmed/33801198 http://dx.doi.org/10.3390/jcm10050984 |
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author | Fleming, Jennifer R. Rani, Alankrita Kraft, Jamie Zenker, Sanja Börgeson, Emma Lange, Stephan |
author_facet | Fleming, Jennifer R. Rani, Alankrita Kraft, Jamie Zenker, Sanja Börgeson, Emma Lange, Stephan |
author_sort | Fleming, Jennifer R. |
collection | PubMed |
description | Three members of the obscurin protein family that contain tandem kinase domains with important signaling functions for cardiac and striated muscles are the giant protein obscurin, its obscurin-associated kinase splice isoform, and the striated muscle enriched protein kinase (SPEG). While there is increasing evidence for the specific roles that each individual kinase domain plays in cross-striated muscles, their biology and regulation remains enigmatic. Our present study focuses on kinase domain 1 and the adjacent low sequence complexity inter-kinase domain linker in obscurin and SPEG. Using Phos-tag gels, we show that the linker in obscurin contains several phosphorylation sites, while the same region in SPEG remained unphosphorylated. Our homology modeling, mutational analysis and molecular docking demonstrate that kinase 1 in obscurin harbors all key amino acids important for its catalytic function and that actions of this domain result in autophosphorylation of the protein. Our bioinformatics analyses also assign a list of putative substrates for kinase domain 1 in obscurin and SPEG, based on the known and our newly proposed phosphorylation sites in muscle proteins, including obscurin itself. |
format | Online Article Text |
id | pubmed-7957886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79578862021-03-16 Exploring Obscurin and SPEG Kinase Biology Fleming, Jennifer R. Rani, Alankrita Kraft, Jamie Zenker, Sanja Börgeson, Emma Lange, Stephan J Clin Med Article Three members of the obscurin protein family that contain tandem kinase domains with important signaling functions for cardiac and striated muscles are the giant protein obscurin, its obscurin-associated kinase splice isoform, and the striated muscle enriched protein kinase (SPEG). While there is increasing evidence for the specific roles that each individual kinase domain plays in cross-striated muscles, their biology and regulation remains enigmatic. Our present study focuses on kinase domain 1 and the adjacent low sequence complexity inter-kinase domain linker in obscurin and SPEG. Using Phos-tag gels, we show that the linker in obscurin contains several phosphorylation sites, while the same region in SPEG remained unphosphorylated. Our homology modeling, mutational analysis and molecular docking demonstrate that kinase 1 in obscurin harbors all key amino acids important for its catalytic function and that actions of this domain result in autophosphorylation of the protein. Our bioinformatics analyses also assign a list of putative substrates for kinase domain 1 in obscurin and SPEG, based on the known and our newly proposed phosphorylation sites in muscle proteins, including obscurin itself. MDPI 2021-03-02 /pmc/articles/PMC7957886/ /pubmed/33801198 http://dx.doi.org/10.3390/jcm10050984 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fleming, Jennifer R. Rani, Alankrita Kraft, Jamie Zenker, Sanja Börgeson, Emma Lange, Stephan Exploring Obscurin and SPEG Kinase Biology |
title | Exploring Obscurin and SPEG Kinase Biology |
title_full | Exploring Obscurin and SPEG Kinase Biology |
title_fullStr | Exploring Obscurin and SPEG Kinase Biology |
title_full_unstemmed | Exploring Obscurin and SPEG Kinase Biology |
title_short | Exploring Obscurin and SPEG Kinase Biology |
title_sort | exploring obscurin and speg kinase biology |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957886/ https://www.ncbi.nlm.nih.gov/pubmed/33801198 http://dx.doi.org/10.3390/jcm10050984 |
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