Phospholipase D2 Directly Interacts with Aldolase via Its PH Domain

Kim, Jong Hyun; Lee, Sukmook; Kim, Junghwan; Lee, Taehoon G.; Hirata, Masato; Suh, Pann Ghill; Ryu, Sung Ho

doi:10.1021/bi015700a

Cited by 76 publications

(59 citation statements)

References 26 publications

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“…Molecular analysis of the interaction between endogenous Grb2 and PLD2 mutants revealed that (Xu et al, 2001), whereas residue Y 179 is conserved only in the PX domain of mammalian PLDs. The N-terminal region of PLD2, containing the PX (a.a. and domains, is the most representative region involved in PLD2 protein-protein interactions (Park et al, 2000;Kim et al, 2002;Ahn et al, 2003;Jang et al, 2003). The relevance of the PX domain is illustrated by the fact that its deletion from PLD2 produces a catalytically inactive enzyme in vitro (Sung et al, 1999;Park et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

The elucidation of novel SH2 binding sites on PLD2

et al. 2006

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Section: Discussionmentioning

confidence: 99%

The elucidation of novel SH2 binding sites on PLD2

et al. 2006

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“…We examined the possibility of a protein-protein interaction between the PH domain and the CTD of ADL6 as a means by which the CTD could affect the lipid binding specificity of the PH domain. Recently it has been shown that the PH domain is also involved in protein-protein interactions (39,40). Interestingly, there was a strong interaction between the PH domain and the CTD at low salt concentrations.…”

Section: Fig 2 Expression and Purification Of Recombinant Proteinsmentioning

confidence: 99%

The Intermolecular Interaction between the PH Domain and the C-terminal Domain of Arabidopsis Dynamin-like 6 Determines Lipid Binding Specificity

Lee

Jin

Song

et al. 2002

Journal of Biological Chemistry

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Dynamin and its related proteins are a group of mechanochemical proteins involved in the modulation of lipid membranes in various biological processes. Here we investigate the nature of membrane binding of the Arabidopsis dynamin-like 6 (ADL6) involved in vesicle trafficking from the trans-Golgi network to the central vacuole. Fractionation experiments by continuous sucrose gradients and gel filtration revealed that the majority of ADL6 is associated with membranes in vivo. Amino acid sequence analysis revealed that ADL6 has a putative pleckstrin homology (PH) domain. In vitro lipid binding assays demonstrated that ADL6 showed high affinity binding to phosphatidylinositol 3-phosphate (PtdIns-3-P) and that the PH domain was responsible for this interaction. However, the PH domain alone binds equally well to both PtdIns-3-P and phosphatidylinositol 4-phosphate (PtdIns-4-P). Interestingly, the high affinity binding of the PH domain to PtdIns-3-P was restored by a protein-protein interaction between the PH domain and the C-terminal region. In addition, deletion of the inserted regions within the PH domain results in high affinity binding of the PH domain to PtdIns-3-P. These results suggest that ADL6 binds specifically to PtdIns-3-P and that the lipid binding specificity is determined by the interaction between the PH domain and the Cterminal domain of ADL6.

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“…For example, PLD2 activity may be modulated in vivo by inhibition (11). The reported inhibitors include a heat-stable 18-kDa protein (11), adolase (13), ceramide (14), ␣-actinin (15), and ␣-and ␤-synucleins (16). On the other hand, a lot of activators of PLD2 activity have also been found.…”

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Regulation of Phospholipase D2 Activity by Protein Kinase Cα

Chen

Exton

2004

Journal of Biological Chemistry

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It has been well documented that protein kinase C (PKC) plays an important role in regulation of phospholipase D (PLD) activity. Although PKC regulation of PLD1 activity has been studied extensively, the role of PKC in PLD2 regulation remains to be established. In the present study it was demonstrated that phorbol 12-myristate 13-acetate (PMA) induced PLD2 activation in COS-7 cells. PLD2 was also phosphorylated on both serine and threonine residues after PMA treatment. PKC inhibitors Ro-31-8220 and bisindolylmaleimide I inhibited both PMA-induced PLD2 phosphorylation and activation. However, Gö 6976, a PKC inhibitor relatively specific for conventional PKC isoforms, almost completely abolished PLD2 phosphorylation by PMA but only slightly inhibited PLD2 activation. Furthermore, time course studies showed that phosphorylation of PLD2 lagged behind its activation by PMA. Concentration curves for PMA action on PLD2 phosphorylation and activation also showed that PLD2 was activated by PMA at concentrations at which PMA didn't induce phosphorylation. A kinase-deficient mutant of PKC␣ stimulated PLD2 activity to an even higher level than wild type PKC␣. Co-expression of wild type PKC␣, but not PKC␦, greatly enhanced both basal and PMA-induced PLD2 phosphorylation. A PKC␦-specific inhibitor, rottlerin, failed to inhibit PMA-induced PLD2 phosphorylation and activation. Co-immunoprecipitation studies indicated an association between PLD2 and PKC␣ under basal conditions that was further enhanced by PMA. Time course studies of the effects of PKC␣ on PLD2 showed that as the phosphorylation of PLD2 increased, its activity declined. In summary, the data demonstrated that PLD2 is activated and phosphorylated by PMA and PKC␣ in COS-7 cells. However, the phosphorylation is not required for PKC␣ to activate PLD2. It is suggested that interaction rather than phosphorylation underscores the activation of PLD2 by PKC in vivo and that phosphorylation may contribute to the inactivation of the enzyme.Phospholipase D (PLD) 1 catalyzes the hydrolysis of phosphatidylcholine (PC) to phosphatidic acid (PA), and choline (1). PA is an important "second messenger" in several physiological processes (2). PA can be further metabolized to diacylglycerol by PA phosphohydrolase or to lysophosphatidic acid by phospholipase A2. Diacylglycerol is a well known activator of protein kinase C (PKC), whereas lysophosphatidic acid mediates many important physiological functions via its G protein-coupled receptors (3). Thus, PLD influences many important intracellular events via producing these downstream products. PLD activity is regulated by many stimuli such as growth factors, cytokines, hormones, neurotransmitters, and other molecules involved in extracellular communication (1). PLD is thought to play an important role in secretion, membrane trafficking, cytoskeleton reorganization, and apoptosis (1).PLD1 and PLD2 are two isoforms of mammalian PLD that share about 50% amino acid similarity. However, their regulatory properties are quite different, e.g. t...

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Phospholipase D2 Directly Interacts with Aldolase via Its PH Domain

Cited by 76 publications

References 26 publications

The elucidation of novel SH2 binding sites on PLD2

The elucidation of novel SH2 binding sites on PLD2

The Intermolecular Interaction between the PH Domain and the C-terminal Domain of Arabidopsis Dynamin-like 6 Determines Lipid Binding Specificity

Regulation of Phospholipase D2 Activity by Protein Kinase Cα

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