Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization

William C. Colley, Tsung Chang Sung, Richard Roll, John Jenco, Scott M. Hammondt, Yelena Altshuller, Dafna Bar-Sagi, Andrew J. Morris, Michael A. Frohman

Research output: Contribution to journalArticlepeer-review

631 Scopus citations

Abstract

Background: Activation of phospholipase D (PLD) is an important but poorly understood component of receptor-mediated signal trensduction responses and regulated secretion. We recently reported the cloning of the human gene encoding PLD1; this enzyme has low basal activity end is activated by protein kinase C and the small GTP-binding proteins, ADP-ribosylation factor (ARF), Rho, Rac and Cdc42. Biochemical and cell biological studies suggest, however, that additional and distinct PLD activities exist in cells, so a search was carried out for novel mammalian genes related to PLD1. Results: We have cloned the gene for a second PLD family member and characterized the protein product, which appears to be regulated differently from PLD1: PLD2 is constitutively active and may be modulated in vivo by inhibition. Unexpectedly, PLD2 localizes primarily to the plasma membrane, in contrast to PLD1 which localizes solely to peri-nuclear regions (the endoplasmic reticulum, Golgi apparatus and late endosomes), where PLD activity has been shown to promote ARF mediated coated-vesicle formation. PLD2 provokes cortical reorganization and undergoes redistribution in serum-stimulated cells, suggesting that it may have a role in signal-induced cytoskeletal regulation and/or endocytosis. Conclusions: PLD2 is e newly identified mammalian PLD isoform with novel regulatory properties. Our findings suggest that regulated secretion and morphological reorganization, the two most frequently proposed biological roles for PLD, are likely to be effected separately by PLD1 and PLD2.

Original languageEnglish
Pages (from-to)191-201
Number of pages11
JournalCurrent Biology
Volume7
Issue number3
DOIs
StatePublished - 1997

Bibliographical note

Funding Information:
The authors thank S. Tsirka, J. Engebrecht, and Y. Zhang for critical reading of the manuscript. This work was supported by grants from the National Institute of Health to A.J.M. (GM50388), D.B. (CA55360), and M.A.F. (HD29758). S.M.H. was supported by a National Institute of Health Training Grant (GM07518) to the Pharmacology Graduate Program.

ASJC Scopus subject areas

  • Neuroscience (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Agricultural and Biological Sciences (all)

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