Structural analysis of human phospholipase D1

Tsung Chang Sung, Yue Zhang, Andrew J. Morris, Michael A. Frohman

Research output: Contribution to journalArticlepeer-review

151 Scopus citations


Activation of phosphatidylcholine-specific phospholipase D (PLD) has been proposed to play roles in numerous cellular pathways including signal transduction and membrane vesicular trafficking. We previously reported the cloning of two mammalian genes, PLD1 and PLD2, that encode PLD activities. We additionally reported that PLD1 is activated in a synergistic manner by protein kinase c-α (PKC-α), ADP-ribosylation factor 1 (ARF1), and Rho family members. We describe here molecular analysis of PLD1 using a combination of domain deletion and mutagenesis. We show that the amino- terminal 325 amino acids are required for PKC-α activation of PLD1 but not for activation by ARF1 and RhoA. This region does not contain the sole PKC- α interaction site and additionally functions to inhibit basal PLD activity in vivo. Second, a region of sequence unique to PLD1 (as compared with other PLDs) known as the 'loop' region had been proposed to serve as an effector regulatory region but is shown here only to mediate inhibition of PLD1. Finally, we show that modification of the amino terminus, but not of the carboxyl terminus, is compatible with PLD enzymatic function and propose a simple model for PLD activation.

Original languageEnglish
Pages (from-to)3659-3666
Number of pages8
JournalJournal of Biological Chemistry
Issue number6
StatePublished - Feb 5 1999

Bibliographical note

Copyright 2007 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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