Unc119 protects from Shigella infection by inhibiting the Abl family kinases.

Article Details

Citation

Vepachedu R, Karim Z, Patel O, Goplen N, Alam R

Unc119 protects from Shigella infection by inhibiting the Abl family kinases.

PLoS One. 2009;4(4):e5211. doi: 10.1371/journal.pone.0005211. Epub 2009 Apr 17.

PubMed ID
19381274 [ View in PubMed
]
Abstract

BACKGROUND: Bacteria engage cell surface receptors and intracellular signaling molecules to enter the cell. Unc119 is an adaptor protein, which interacts with receptors and tyrosine kinases. Its role in bacterial invasion of cells is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used biochemical, molecular and cell biology approaches to identify the binding partners of Unc119, and to study the effect of Unc119 on Abl family kinases and Shigella infection. We employed loss-of-function and gain-in-function approaches to study the effect of Unc119 in a mouse model of pulmonary shigellosis. Unc119 interacts with Abl family kinases and inhibits their kinase activity. As a consequence, it inhibits Crk phosphorylation, which is essential for Shigella infection. Unc119 co-localizes with Crk and Shigella in infected cells. Shigella infectivity increases in Unc119-deficient epithelial and macrophage cells. In a mouse model of shigellosis cell-permeable TAT-Unc119 inhibits Shigella infection. Conversely, Unc119 knockdown in vivo results in enhanced bacterial invasion and increased lethality. Unc119 is an inducible protein. Its expression is upregulated by probacteria and bacterial products such as lipopolysacharide and sodium butyrate. The latter inhibits Shigella infection in mouse lungs but is ineffective in Unc119 deficiency. CONCLUSIONS: Unc119 inhibits signaling pathways that are used by Shigella to enter the cell. As a consequence it provides partial but significant protection from Shigella infections. Unc119 induction in vivo boosts host defense against infections.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Tyrosine-protein kinase ABL1P00519Details
Abelson tyrosine-protein kinase 2P42684Details
CD44 antigenP16070Details