Page 38 - D. Cancer biology

[D. Cancer biology-27]

Pleckstrin homology domain of phospholipase D2 has anti-

tumorigenic role via negative regulation of phospholipase D2

and focal adhesion kinase

RaeHee kang¹, WonChan Hwang¹, Venu Venkatarame Gowda Saralamma¹, JuWon Kim¹, MinJu Kang¹,

Hyun Ji Lee¹, DoSik Min¹

¹College of Pharmacy, Yonsei University, InCheon 21983, Republic of Korea

Phospholipase D2 (PLD2) isozyme has been implicated in mitogenic tyrosine kinase-mediated-signaling pathways.

Here, we show that PLD2 isozyme is tyrosine phosphorylated by mitogenic focal adhesion tyrosine kinase (FAK)
through its interaction. Kinase domain of FAK binds to pleckstrin homology (PH) domain of PLD2 (PLD2-PH), and

stimulates PLD activity via protein-protein interaction. PLD2-PH reduced the interaction of PLD2 with FAK probably
through its competition with FAK, and suppressed FAK-induced PLD activation. Moreover, PLD2 increased tyrosine

phosphorylation of FAK in a lipase activity-independent manner. Furthermore, PLD2-PH reduced tyrosine
phosphorylation of FAK and its downstream molecules, paxillin and ERK. Although FAK and PLD2 increased migration

and invasion of U87MG glioblastoma cells, PLD2-PH significantly suppressed migration and invasion of the cancer
cells and tumor formation in xenografted mice model. Collectively, these results suggest that positive feedback loop

of PLD2 and FAK contribute to the promotion of oncogenic effects and PLD2-PH is a negative regulator of FAK.