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Autoimmunity-associated DIORA1 binds the MRCK family of serine/threonine kinases and controls cell motility

ABSTRACT: Genetic association links DIORA1 to numerous autoimmune rheumatic diseases including systemic lupus erythematous, Sjögren's disease, myositis, scleroderma and rheumatoid arthritis, but its cellular function remains unknown. Here, we identify the MRCK kinase family as DIORA1 interactors. MRCK kinases regulate the activity of actin-myosin networks, including cell adhesion, motility and invasion. Mapping the interaction between DIORA1 and MRCKs, we found that DIORA1 binds three distinct modules of MRCK kinases, including the conserved autoinhibitory kinase inhibitory motif (KIM) and C1-PH-CNH domains. Knockdown of DIORA1 altered cellular phosphorylation patterns, including reduced phosphorylation of known MRCK targets. Functional analyses revealed enhanced cellular migration and invasion following knockdown of DIORA1, and RNA-sequencing and proteomic analyses confirmed upregulation of epithelial mesenchymal transition genes and proteins. In summary, our findings identify autoimmunity-associated DIORA1 as a previously uncharacterized interactor of MRCK kinases and a modulator of cell motility.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Akos Vegvari

LAB HEAD: Akos Vegvari

PROVIDER: PXD064939 | Pride | 2025-09-08

REPOSITORIES: Pride

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			Action	DRS
	20190225_F_03_Tilen_Beads_BiolD2_1_Diora.raw	Raw
	20190225_F_03_Tilen_Beads_BiolD2_1_Diora_F039272.csv	Csv
	20190225_F_04_Tilen_Beads_BiolD2_2_Ctrl.raw	Raw
	20190225_F_04_Tilen_Beads_BiolD2_2_Ctrl_F039273.csv	Csv
	20200617_L1_02_Tilen_200612_Beads_Control.raw	Raw

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