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Phospholipases in Health and Disease pp 359–379Cite as

Emerging Roles of Phospholipase D in Pathophysiological Signaling

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Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 10))

Abstract

Phospholipase D (PLD) is a phospholipid-hydrolyzing enzyme that generates phosphatidic acid (PA) as a lipid second messenger by hydrolyzing phosphatidyl choline (PC). Various extracellular signals have been reported to activate PLD, which acts as a key mediator of many cellular functions through the generation of PA and the interactions of PLD and PA with their binding partners. Currently, about 60 PLD-binding partners, including proteins and phospholipids, are known, and PA has been found to interact with about 50 proteins. Although the interactions of binding molecules with PLD and PA are complex and multilayered, the unique interactions between them are important for their unique intracellular functions. Here, we address the interrelationships between PLD and PA and their binding partners in several key signaling pathways, such as the EGFR–ERK signaling axis, nutrient/growth signaling axis, and cytoskeletal reorganization machinery axis. These interrelationships demonstrate dynamic interactions and cooperative regulation, which mediate special intracellular functions. Furthermore, we describe the regulation and functions of PLD in mediating normal and pathological signaling. Additionally, we summarize the roles of PLD as determined in animal studies (Drosophila, zebrafish, and mice) and changes in the PLD expression level in disease states. These findings provide new insight into the functions of PLD under pathophysiological conditions.

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Acknowledgments

This work was supported by the grants (No. 2012R1A2A1A03010110 and NRF‑M1AXA002‑2010‑0029764) of National Research Foundation funded by the Ministry of Education Science and Technology of Korea.

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    Authors and Affiliations

    1. Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea

      Chang Sup Lee, Jaewang Ghim, Hyeona Jeon & Sung Ho Ryu

    2. Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, 1340 JPA, Charlottesville, VA, 22908, USA

      Chang Sup Lee

    3. School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea

      Jin-Hyeok Jang & Sung Ho Ryu

    4. School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, 689-798, Republic of Korea

      Pann-Ghill Suh

    5. Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea

      Sung Ho Ryu

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    1. Chang Sup Lee
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    Correspondence to Sung Ho Ryu .

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    1. I.H. Asper Clinical Research Institute St. Boniface Hospital Research, Winnipeg, Manitoba, Canada

      Paramjit S. Tappia

    2. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

      Naranjan S. Dhalla

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    Lee, C.S., Ghim, J., Jang, JH., Jeon, H., Suh, PG., Ryu, S.H. (2014). Emerging Roles of Phospholipase D in Pathophysiological Signaling. In: Tappia, P., Dhalla, N. (eds) Phospholipases in Health and Disease. Advances in Biochemistry in Health and Disease, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0464-8_22

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