Pleckstrin homology domain of phospholipase D2 is a negative regulator of focal adhesion kinase

Mi Kyoung Kim; Won Chan Hwang; Do Sik Min

doi:10.5483/BMBRep.2021.54.2.154

Pleckstrin homology domain of phospholipase D2 is a negative regulator of focal adhesion kinase

Mi Kyoung Kim, Won Chan Hwang, Do Sik Min

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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.

Original language	English
Pages (from-to)	112-117
Number of pages	6
Journal	BMB reports
Volume	54
Issue number	2
DOIs	https://doi.org/10.5483/BMBRep.2021.54.2.154
Publication status	Published - 2021

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation

Funding Information:
of Korea (NRF) grant funded by the Korean government (NRF-2018R1A2B3002179, 2019M3A9A8065095) and by the Yonsei University Research Fund (2019-22-0193).

Publisher Copyright:
© 2021. by the The Korean Society for Biochemistry and Molecular Biology.

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology

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10.5483/BMBRep.2021.54.2.154

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title = "Pleckstrin homology domain of phospholipase D2 is a negative regulator of focal adhesion kinase",

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.",

author = "Kim, {Mi Kyoung} and Hwang, {Won Chan} and Min, {Do Sik}",

note = "Funding Information: This work was supported by a National Research Foundation Funding Information: of Korea (NRF) grant funded by the Korean government (NRF-2018R1A2B3002179, 2019M3A9A8065095) and by the Yonsei University Research Fund (2019-22-0193). Publisher Copyright: {\textcopyright} 2021. by the The Korean Society for Biochemistry and Molecular Biology.",

year = "2021",

doi = "10.5483/BMBRep.2021.54.2.154",

language = "English",

volume = "54",

pages = "112--117",

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AU - Kim, Mi Kyoung

AU - Hwang, Won Chan

AU - Min, Do Sik

N1 - Funding Information: This work was supported by a National Research Foundation Funding Information: of Korea (NRF) grant funded by the Korean government (NRF-2018R1A2B3002179, 2019M3A9A8065095) and by the Yonsei University Research Fund (2019-22-0193). Publisher Copyright: © 2021. by the The Korean Society for Biochemistry and Molecular Biology.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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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Pleckstrin homology domain of phospholipase D2 is a negative regulator of focal adhesion kinase

Abstract

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