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.
|Number of pages||6|
|Publication status||Published - 2021|
Bibliographical noteFunding Information:
This work was supported by a National Research Foundation
of Korea (NRF) grant funded by the Korean government (NRF-2018R1A2B3002179, 2019M3A9A8065095) and by the Yonsei University Research Fund (2019-22-0193).
© 2021. by the The Korean Society for Biochemistry and Molecular Biology.
All Science Journal Classification (ASJC) codes
- Molecular Biology