Trselic, Tilen and Pelo, Nathalie and de Fremont, Gregoire Martin and Iyer, Vaishnavi S. and Andersson, Elina Richardsdotter and Ottosson, Vijole and Frei, David Alexander and Baas, Elisa and Nyberg, William A. and Thorlacius, Gudny Ella and Mentlein, Lara and Boddul, Sanjaykumar and Sandu, Ioana and Pulgarin, Diego Velasquez and Vegvari, Akos and Gerlach, Carmen and Wermeling, Fredrik and Sunnerhagen, Maria and Wallner, Bjorn and Espinosa, Alexander and Wahren-Herlenius, Marie (2025) Autoimmunity- associated DIORA1 binds the MRCK family of serine/threonine kinases and controls cell motility. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 122 (40): e242691712. ISSN 0027-8424, 1091-6490
Full text not available from this repository. (Request a copy)Abstract
Genetic association links disordered autoimmunity 1 (DIORA1) to numerous auto-immune rheumatic diseases, including systemic lupus erythematosus, Sj & ouml;gren's disease, rheumatoid arthritis, polymyositis, and systemic sclerosis. However, its cellular function has remained unknown. Here, we identify the Myotonic Dystrophy Kinase-Related Cdc42-Binding Kinases (MRCK kinases) family of serine/threonine kinases-key regulators of actomyosin contractility and cell motility-as direct inter-actors of DIORA1. Through interaction mapping, we show that DIORA1 binds three distinct modules of MRCK kinases, including the conserved kinase inhibitory motif, C1-PH, and citron homology domains. DIORA1 knockdown in human cells altered cellular phosphorylation patterns and reduced phosphorylation of known MRCK targets. RNA-sequencing and proteomic analyses revealed upregulation of epithelial-mesenchymal transition genes and proteins, and functional analyses confirmed increased cell invasion, following knockdown of DIORA1. Together, these findings identify the autoimmunity-associated DIORA1 protein as an interactor of MRCK kinases and a regulator of cell motility.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHOSPHORYLATION; PROTEIN; ROCK; ACTIVATION; ROLES; LOCI; GENE; DIORA1; FAM167A; autoimmunity; MRCKkinases; cell motility |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2026 11:43 |
| Last Modified: | 28 Jul 2026 11:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67268 |
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