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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Pleckstrin homology domain of phospholipase D2 is a negative regulator of focal adhesion kinase

  • Kim, Mi Kyoung (Department of Molecular Biology, College of Natural Science, Pusan National University) ;
  • Hwang, Won Chan (Department of Molecular Biology, College of Natural Science, Pusan National University) ;
  • Min, Do Sik (College of Pharmacy, Yonsei University)
  • Received : 2020.07.21
  • Accepted : 2020.08.19
  • Published : 2021.02.28
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Abstract

Phospholipase D2 (PLD2) has been implicated in the tyrosine kinase-mediated signaling pathways, but the regulation events are yet to be identified. Herein, we demonstrate that pleckstrin homology (PH) domain of PLD2 (PLD2-PH) exerts an antitumorigenic effect via the suppression of PLD2 and focal adhesion kinase (FAK). The kinase domain of FAK interacts with PLD2-PH and induces tyrosine phosphorylation and activation of PLD2. Furthermore, PLD2 increased tyrosine phosphorylation of FAK. However, ectopic expression of the PLD2-PH competes for binding to FAK and reduces the interaction between PLD2 and FAK, thereby suppressing FAK-induced PLD activation and tyrosine phosphorylation of FAK. The PLD2-PH suppressed the migration and invasion of glioblastoma cells, as well as tumor formation in a xenograft mouse model. This study uncovers a novel role of PLD2-PH as a negative regulator of PLD2 and FAK.

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References

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