Diacylglycerol Kinase γ Is One of the Specific Receptors of Tumor-Promoting Phorbol Esters

Shindo, Mayumi; Irie, Kazuhiro; Ohigashi, Hajime; Kuriyama, Masami; Saito, Naoaki

doi:10.1006/bbrc.2001.5935

Cited by 40 publications

(33 citation statements)

References 27 publications

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“…However, the fact that PKC and -⑀ are able to interact with and phosphorylate DGK in vitro may suggest that the regulation is more direct. Since TPA-induced DGK translocation was fully prevented by PKC inhibitors, we can exclude the possibility that TPA directly recruits DGK to the membrane via its CRD(s), as described for the DGK␥ isotype (33,34). It was therefore unexpected that the DAG analog (and PKC activator) DiC8 induced DGK translocation independent of PKC activity, the more so as DiC8 was unable to induce DGK␣ translocation in a different cell system (57).…”

Section: Discussionmentioning

confidence: 95%

“…First, similar to PKC, DAG, generated by PLC in the plasma membrane or the nucleus, may potentially recruit DGK through binding to its CRDs (32). Indeed, the CRDs of DGK␥ and possibly DGK␤ interact with the DAG substitute, phorbol ester (12-O-tetradecanoylphorbol-13-acetate (TPA)) (33,34). Furthermore, an undefined DGK activity translocated to artificially enhanced DAG in membranes of some cell systems (reviewed in Ref.…”

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confidence: 99%

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Translocation of Diacylglycerol Kinase θ from Cytosol to Plasma Membrane in Response to Activation of G Protein-coupled Receptors and Protein Kinase C

Baal

Widt

Divecha

et al. 2005

Journal of Biological Chemistry

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Diacylglycerol kinase (DGK) phosphorylates the second messenger diacylglycerol (DAG) to phosphatidic acid. We previously identified DGK as one of nine mammalian DGK isoforms and reported on its regulation by interaction with RhoA and by translocation to the plasma membrane in response to noradrenaline. Here, we have investigated how the localization of DGK, fused to green fluorescent protein, is controlled upon activation of G protein-coupled receptors in A431 cells. Extracellular ATP, bradykinin, or thrombin induced DGK translocation from the cytoplasm to the plasma membrane within 2-6 min. This translocation, independent of DGK activity, was preceded by protein kinase C (PKC) translocation and was blocked by PKC inhibitors. Conversely, activation of PKC by 12-O-tetradecanoylphorbol-13-acetate induced DGK translocation. Membrane-permeable DAG (dioctanoylglycerol) also induced DGK translocation but in a PKC (staurosporin)-independent fashion. Mutations in the cysteinerich domains of DGK abrogated its hormone-and DAGinduced translocation, suggesting that these domains are essential for DAG binding and DGK recruitment to the membrane. We show that DGK interacts selectively with and is phosphorylated by PKC⑀ and -and that peptide agonist-induced selective activation of PKC⑀ directly leads to DGK translocation. Our data are consistent with the concept that hormone-induced PKC activation regulates the intracellular localization of DGK, which may be important in the negative regulation of PKC⑀ and/or PKC activity.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Translocation of Diacylglycerol Kinase θ from Cytosol to Plasma Membrane in Response to Activation of G Protein-coupled Receptors and Protein Kinase C

Baal

Widt

Divecha

et al. 2005

Journal of Biological Chemistry

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“…Plasmid Construction for FLAG-tagged Rat-DGK␥-The plasmid for FLAG-tagged DGK␥-(1-789) (FLAG-DGK␥) was generated by PCR using BS412 (rat-DGK␥) as a template as reported previously (28 (28). After transfection, the cells were cultured at 37°C for 48 h and were harvested with phosphate-buffered saline(Ϫ), followed by centrifugation at 600 ϫ g for 5 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Phorbol Ester Binding of the Cysteine-rich Domains of Diacylglycerol Kinase (DGK) Isozymes

Shindo¹,

Irie

Masuda

et al. 2003

Journal of Biological Chemistry

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Diacylglycerol kinase (DGK) and protein kinase C (PKC) are two distinct enzyme families associated with diacylglycerol. Both enzymes have cysteine-rich C1 domains (C1A, C1B, and C1C) in the regulatory region. Although most PKC C1 domains strongly bind phorbol esters, there has been no direct evidence that DGK C1 domains bind phorbol esters. We synthesized 11 cysteine-rich sequences of DGK C1 domains with good sequence homology to those of the PKC C1 domains. Among them, only DGK␥-C1A and DGK␤-C1A exhibited significant binding to phorbol 12,13-dibutyrate (PDBu). Scatchard analysis of rat-DGK␥-C1A, human-DGK␥-C1A, and human-DGK␤-C1A gave K d values of 3.6, 2.8, and 14.6 nM, respectively, suggesting that DGK␥ and DGK␤ are new targets of phorbol esters. An A12T mutation of human-DGK␤-C1A enhanced the affinity to bind PDBu, indicating that the ␤-hydroxyl group of Thr-12 significantly contributes to the binding. The K d value for PDBu of FLAG-tagged whole rat-DGK␥ (4.4 nM) was nearly equal to that of rat-DGK␥-C1A (3.6 nM). Moreover, 12-O-tetradecanoylphorbol 13-acetate induced the irreversible translocation of whole rat-DGK␥ and its C1B deletion mutant, not the C1A deletion mutant, from the cytoplasm to the plasma membrane of CHO-K1 cells. These results indicate that 12-O-tetradecanoylphorbol 13-acetate binds to C1A of DGK␥ to cause its translocation.Diacylglycerol kinase (DGK) 1 and protein kinase C (PKC) both interact with the second messenger diacylglycerol (DG) (1, 2). DGK phosphorylates DG to produce phosphatidic acid, whereas PKC is allosterically activated by DG in the presence of phosphatidylserine. Therefore, DGK may inhibit the activation of PKC by attenuating DG levels, contributing to the regulation of intracellular signal transduction.To date, nine subtypes of mammalian DGKs have been cloned (3-15). All DGK isozymes consist of a conserved catalytic domain and two or three cysteine-rich C1 domains designated as C1A, C1B, and C1C (16). These isozymes are classified into five classes according to the other functional domains (Fig. 1). The class I isozymes (DGK␣, -␤, and -␥) have calcium binding domains (EF-hands). The class II isozymes (DGK␦ and -) have a pleckstrin homology domain at the N terminus, and their catalytic region is split into two domains unlike the other DGK isozymes. DGK⑀ has a simple structure and is classified as a class III isozyme. The class IV isozymes DGK and have a myristoylated alanine-rich C kinase substrate homology domain and four ankyrin repeats. DGK , which has three C1 domains unlike other DGK and PKC isozymes, is the only isozyme in class V.The similarity between DGK and PKC isozymes in structure is in the cysteine-rich C1 domains. Recent investigations using NMR spectroscopy and x-ray crystallography have revealed the three-dimensional structure of C1B domains of PKC␣, PKC␥,. Each PKC C1 domain has six conserved cysteines and two histidines in the typical core structure HX 12 CX 2 CX 13-14 CX 2 CX 4 HX 2 CX 7 C (where X is any amino acid) that coordinates two atoms of zinc in...

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“…C-1 sites are also found in regulators of lowmolecular-weight G-proteins (RAS-GRP and chimaerins), in Munc-13 (a protein involved in vesicle cycling) and in several DGK isoforms (Ron and Kazanietz, 1999;Topham and Prescott, 1999;van Blitterswijk and Houssa, 2000;Shindo et al, 2001;Brose and Rosenmund, 2002;Kanoh et al, 2002;Kazanietz, 2002;Topham and Prescott, 2002;Shindo et al, 2003;Yang and Kazanietz, 2003).…”

Section: Activation Of Dgks Contributes To 4␤pma Facilitation Of Hcn mentioning

confidence: 99%

HCN Pacemaker Channel Activation Is Controlled by Acidic Lipids Downstream of Diacylglycerol Kinase and Phospholipase A2

Fogle¹,

Lyashchenko²,

Turbendian³

et al. 2007

J. Neurosci.

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Diacylglycerol Kinase γ Is One of the Specific Receptors of Tumor-Promoting Phorbol Esters

Cited by 40 publications

References 27 publications

Translocation of Diacylglycerol Kinase θ from Cytosol to Plasma Membrane in Response to Activation of G Protein-coupled Receptors and Protein Kinase C

Translocation of Diacylglycerol Kinase θ from Cytosol to Plasma Membrane in Response to Activation of G Protein-coupled Receptors and Protein Kinase C

Synthesis and Phorbol Ester Binding of the Cysteine-rich Domains of Diacylglycerol Kinase (DGK) Isozymes

HCN Pacemaker Channel Activation Is Controlled by Acidic Lipids Downstream of Diacylglycerol Kinase and Phospholipase A2

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