ArticleThe Journal of biological chemistry2013
Myosin 3A kinase activity is regulated by phosphorylation of the kinase domain activation loop.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Characterization of a novel MYO3A missense mutation associated with a dominant form of late onset hearing loss.Scientific reports · 2018Trial
- Exploring phosphoregulation of MYO3A using quantitative fluorescence image analysis in COS7 cells.microPublication biology · 2026Article
- Structural and functional mechanisms of actin isoforms.The FEBS journal · 2025Review
- The Prevalence and Clinical Characteristics ofGenes · 2025Article
- Functional annotation of the Hippo pathway somatic mutations in human cancers.Nature communications · 2024Article
- The dynamics of actin protrusions can be controlled by tip-localized myosin motors.The Journal of biological chemistry · 2024Article
- Pathophysiology of human hearing loss associated with variants in myosins.Frontiers in physiology · 2024Review
- The Hippo pathway noncanonically drives autophagy and cell survival in response to energy stress.Molecular cell · 2023Article
- Selective binding and transport of protocadherin 15 isoforms by stereocilia unconventional myosins in a heterologous expression system.Scientific reports · 2022Article
- STE20 phosphorylation of AMPK-related kinases revealed by biochemical purifications combined with genetics.The Journal of biological chemistry · 2022Article
- Deafness mutation in the MYO3A motor domain impairs actin protrusion elongation mechanism.Molecular biology of the cell · 2022Article
- Identification of transcriptional regulatory network associated with response of host epithelial cells to SARS-CoV-2.Scientific reports · 2021Article
- The many roles of myosins in filopodia, microvilli and stereocilia.Current biology : CB · 2021Review
- Functional Role of Class III Myosins in Hair Cells.Frontiers in cell and developmental biology · 2021Review
- Myosin XVI in the Nervous System.Cells · 2020Review
- Knock-In Mice with Myo3a Y137C Mutation Displayed Progressive Hearing Loss and Hair Cell Degeneration in the Inner Ear.Neural plasticity · 2018Article
- Impact of the Motor and Tail Domains of Class III Myosins on Regulating the Formation and Elongation of Actin Protrusions.The Journal of biological chemistry · 2016Article
- MYO3A Causes Human Dominant Deafness and Interacts with Protocadherin 15-CD2 Isoform.Human mutation · 2016Article
- Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like.Nature communications · 2016Article
- Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Class III myosins are unique members of the myosin superfamily in that they contain both a motor and kinase domain. We have found that motor activity is decreased by autophosphorylation, although little is known about the regulation of the kinase domain. We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919). The kinase activity of MYO3A 2IQ with the phosphomimic (T184E) or phosphoblock (T184A) mutations demonstrates that kinase activity is reduced 30-fold as a result of the T184A mutation, although the Thr-178 site only had a minor impact on kinase activity. Interestingly, the actin-activated ATPase activity of MYO3A 2IQ is slightly reduced as a result of the T178A and T184A mutations suggesting coupling between motor and kinase domains. Full-length GFP-tagged T184A and T184E MYO3A constructs transfected into COS7 cells do not disrupt the ability of MYO3A to localize to filopodia structures. In addition, we demonstrate that T184E MYO3A reduces filopodia elongation in the presence of espin-1, whereas T184A enhances filopodia elongation in a similar fashion to kinase-dead MYO3A. Our results suggest that as MYO3A accumulates at the tips of actin protrusions, autophosphorylation of Thr-184 enhances kinase activity resulting in phosphorylation of the MYO3A motor and reducing motor activity. The differential regulation of the kinase and motor activities allows for MYO3A to precisely self-regulate its concentration in the actin bundle-based structures of cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.