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bioRxiv · 10.1101/2024.08.25.609487

c-Abl Kinase Targets Tight Junction Protein ZO-2 in Regulation of Cell Migration and Morphology

Choi, D. E.·Gweon, B.·Notbohm, J.·Liu, X.-S.·Fredberg, J. J.
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Abstract

c-Abl is a non-receptor tyrosine kinase involved in the regulation of cell migration and morphogenesis, but underlying mechanism remains unclear. Here, we report the identification of tight junction protein ZO-2 as a bona fide substrate of c-Abl. We show that c-Abl directly binds to and phosphorylates the C-terminus of ZO-2. In addition, c-Abl stimulates the activity of JAK1, which subsequently phosphorylates the N-terminus of ZO-2. Using the RNAi-mediated knockdown/rescue strategy, we demonstrate that c-Abl regulates cellular morphology and migration through targeting ZO-2 for phosphorylation. c-Abl activity is also associated with decreased traction forces exerted on the cell substrate and reduced monolayer tension, thus corroborating c-Abl kinase activity-mediated inhibition of cell migration. Collectively, our data uncover ZO-2 as a novel mediator for c-Abl-dependent regulation of cell migration.

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Choi, D. E., Gweon, B., Notbohm, J., Liu, X.-S., Fredberg, J. J.. 2024-08-26. c-Abl Kinase Targets Tight Junction Protein ZO-2 in Regulation of Cell Migration and Morphology. https://doi.org/10.1101/2024.08.25.609487

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