Cargando…
Twitchin kinase inhibits muscle activity
Muscle sarcomeres contain giant polypeptides composed of multiple immunoglobulin and fibronectin domains and one or two protein kinase domains. Although binding partners for a number of this family’s kinase domains have been identified, the catalytic necessity of these kinase domains remains unknown...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469603/ https://www.ncbi.nlm.nih.gov/pubmed/28428253 http://dx.doi.org/10.1091/mbc.E16-10-0707 |
_version_ | 1783243607915888640 |
---|---|
author | Matsunaga, Yohei Hwang, Hyundoo Franke, Barbara Williams, Rhys Penley, McKenna Qadota, Hiroshi Yi, Hong Morran, Levi T. Lu, Hang Mayans, Olga Benian, Guy M. |
author_facet | Matsunaga, Yohei Hwang, Hyundoo Franke, Barbara Williams, Rhys Penley, McKenna Qadota, Hiroshi Yi, Hong Morran, Levi T. Lu, Hang Mayans, Olga Benian, Guy M. |
author_sort | Matsunaga, Yohei |
collection | PubMed |
description | Muscle sarcomeres contain giant polypeptides composed of multiple immunoglobulin and fibronectin domains and one or two protein kinase domains. Although binding partners for a number of this family’s kinase domains have been identified, the catalytic necessity of these kinase domains remains unknown. In addition, various members of this kinase family are suspected pseudokinases with no or little activity. Here we address catalytic necessity for the first time, using the prototypic invertebrate representative twitchin (UNC-22) from Caenorhabditis elegans. In in vitro experiments, change of a conserved lysine (K) that is involved in ATP coordination to alanine (A) resulted in elimination of kinase activity without affecting the overall structure of the kinase domain. The same mutation, unc-22(sf21), was generated in the endogenous twitchin gene. The unc-22(sf21) worms have well-organized sarcomeres. However, unc-22(sf21) mutants move faster than wild-type worms and, by optogenetic experiments, contract more. Wild-type nematodes exhibited greater competitive fitness than unc-22(sf21) mutants. Thus the catalytic activity of twitchin kinase has a role in vivo, where it inhibits muscle activity and is likely maintained by selection. |
format | Online Article Text |
id | pubmed-5469603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-54696032017-08-30 Twitchin kinase inhibits muscle activity Matsunaga, Yohei Hwang, Hyundoo Franke, Barbara Williams, Rhys Penley, McKenna Qadota, Hiroshi Yi, Hong Morran, Levi T. Lu, Hang Mayans, Olga Benian, Guy M. Mol Biol Cell Brief Report Muscle sarcomeres contain giant polypeptides composed of multiple immunoglobulin and fibronectin domains and one or two protein kinase domains. Although binding partners for a number of this family’s kinase domains have been identified, the catalytic necessity of these kinase domains remains unknown. In addition, various members of this kinase family are suspected pseudokinases with no or little activity. Here we address catalytic necessity for the first time, using the prototypic invertebrate representative twitchin (UNC-22) from Caenorhabditis elegans. In in vitro experiments, change of a conserved lysine (K) that is involved in ATP coordination to alanine (A) resulted in elimination of kinase activity without affecting the overall structure of the kinase domain. The same mutation, unc-22(sf21), was generated in the endogenous twitchin gene. The unc-22(sf21) worms have well-organized sarcomeres. However, unc-22(sf21) mutants move faster than wild-type worms and, by optogenetic experiments, contract more. Wild-type nematodes exhibited greater competitive fitness than unc-22(sf21) mutants. Thus the catalytic activity of twitchin kinase has a role in vivo, where it inhibits muscle activity and is likely maintained by selection. The American Society for Cell Biology 2017-06-15 /pmc/articles/PMC5469603/ /pubmed/28428253 http://dx.doi.org/10.1091/mbc.E16-10-0707 Text en © 2017 Matsunaga et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Brief Report Matsunaga, Yohei Hwang, Hyundoo Franke, Barbara Williams, Rhys Penley, McKenna Qadota, Hiroshi Yi, Hong Morran, Levi T. Lu, Hang Mayans, Olga Benian, Guy M. Twitchin kinase inhibits muscle activity |
title | Twitchin kinase inhibits muscle activity |
title_full | Twitchin kinase inhibits muscle activity |
title_fullStr | Twitchin kinase inhibits muscle activity |
title_full_unstemmed | Twitchin kinase inhibits muscle activity |
title_short | Twitchin kinase inhibits muscle activity |
title_sort | twitchin kinase inhibits muscle activity |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469603/ https://www.ncbi.nlm.nih.gov/pubmed/28428253 http://dx.doi.org/10.1091/mbc.E16-10-0707 |
work_keys_str_mv | AT matsunagayohei twitchinkinaseinhibitsmuscleactivity AT hwanghyundoo twitchinkinaseinhibitsmuscleactivity AT frankebarbara twitchinkinaseinhibitsmuscleactivity AT williamsrhys twitchinkinaseinhibitsmuscleactivity AT penleymckenna twitchinkinaseinhibitsmuscleactivity AT qadotahiroshi twitchinkinaseinhibitsmuscleactivity AT yihong twitchinkinaseinhibitsmuscleactivity AT morranlevit twitchinkinaseinhibitsmuscleactivity AT luhang twitchinkinaseinhibitsmuscleactivity AT mayansolga twitchinkinaseinhibitsmuscleactivity AT benianguym twitchinkinaseinhibitsmuscleactivity |