Specificity of the Fatty Acyl Moieties of Diacylglycerol for the Activation of Calcium-Activated, Phospholipid-Dependent Protein Kinase1

Mori, T; Takai, Yoshimi; Yu, Binzu; Takahashi, Juro; Nishizuka, Yasutomi; Fujikura, Takashi

doi:10.1093/oxfordjournals.jbchem.a133714

Cited by 179 publications

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“…In addition to its ability to activate Ba 2ϩ influx through rTRP6A, OAG is also known to activate PKC (46). To determine whether PKC activation is correlated with Ba 2ϩ influx, we examined the effects of another PKC activator, PMA, on Ba 2ϩ influx.…”

Section: Discussionmentioning

confidence: 99%

Muscarinic Acetylcholine Receptor Regulation of TRP6 Ca2+ Channel Isoforms

Zhang

Saffen

2001

Journal of Biological Chemistry

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In this study, we report the molecular cloning of cDNAs encoding three distinct isoforms of rat (r) TRP6 Ca 2؉ channels. The longest isoform, rTRP6A, contains 930 amino acid residues; rTRP6B lacks 54 amino acids (3-56) at the N terminus, and rTRP6C is missing an additional 68 amino acids near the C terminus. influx. Glycosylation analysis indicated that rTRP6A and rTRP6B are glycosylated in COS cells, but that rTRP6C is mostly not glycosylated. Together these results suggest that the N terminus (3-56 amino acids) is crucial for the activation of rTRP6A by diacylglycerol and that the 735-802 amino acid segment located just downstream from the 6th transmembrane segment may be required for processing of the rTRP6 protein.

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Section: Discussionmentioning

confidence: 99%

Muscarinic Acetylcholine Receptor Regulation of TRP6 Ca2+ Channel Isoforms

Zhang

Saffen

2001

Journal of Biological Chemistry

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“…The effect of thrombin on the properties of [14C]serotonin secretion is quantitatively mimicked by addition of an activator of protein kinase C, e.g. OAG, TPA [26,27] but this is not the case for /I-Nacetylglucosaminidase secretion where the extent of enhancement observed on addition of OAG or TPA is smaller than is caused by addition of thrombin (Fig. 6).…”

Section: Discussionmentioning

confidence: 99%

Thrombin and activators of protein kinase C modulate secretory responses of permeabilised human platelets induced by Ca²⁺

Knight

Niggli

Scrutton

1984

European Journal of Biochemistry

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Addition of thrombin enhances secretion of both [14C]serotonin and P-N-acetylglucosaminidase induced by Ca2+ in human platelets rendered permeable by exposure to intense electric fields. 2. Enhancement of P-N-acetylglucosaminidase secretion by thrombin results from an increase in the maximal extent of the response with no significant change in the median effective concentration EC,o for CaZ+. In contrast, thrombin shifts the dose/response curve for Ca2+-induced ['4C]serotonin secretion to the left and has little effect on the maximal extent of this response even when this extent is reduced by use of a non-saturating concentration of MgATP2-. 6. Addition of 1-10 pM Ca2+ to permeabilised platelets in the presence of [y-32P] ATP causes marked enhancement of 32P incorporation into polypeptides of molecular mass 20 kDA, 45 kDA and 66 kDA. NO additional polypeptides become phosphorylated in this system when thrombin is added together with 10 pM Ca2+, but some increase is observed in the extent of phosphorylation of the 45-kDa polypeptide. Addition of 1 -0leyl-2-acetylglycerol + 1 -2 pM Ca2+ causes enhanced phosphorylation of the 45-kDa polypeptide and to a lesser extent of the 20-kDa polypeptide. The dose/response curves for Ca2+-dependent phosphorylation of the 45-kDa polypeptide in the presence and absence of 1 -oleyl-2-acetylglycerol are similar to those observed for CaZ +-dependent [14C]serotonin secretion under these conditions. 7. At 0.01 pM Ca" addition of either thrombin or 1 -oleyl-2-acetylglycerol in the presence of b;-32P] ATP causes enhanced phosphorylation of the 45-kDa polypeptide but not of the 20-kDa or 66-kDa polypeptides without significant release of ['4C]serotonin.8. The results are consistent with the postulate that thrombin enhances [14C]serotonin secretion induced by Ca2' in permeabilised platelets by increasing the level of 1,2-diacylglycerol and hence activating protein kinase C, but that this mechanism is not adequate to explain the enhancement of P-N-acetylglucosaminidase secretion caused by addition of thrombin in this preparation.

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“…We determined the K i values of OAG, bryostatin 1, IL-V, and Ing-3-Bz. OAG is a membrane-permeable analogue of natural diacylglycerols without tumor promoting activity (35). Bryostatin 1 is a macrocyclic lactone with potent antileukemic activity (36).…”

Section: Fig 2 Cysteine-rich Sequences Of All Dgk Isozymes (R Rat;mentioning

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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Specificity of the Fatty Acyl Moieties of Diacylglycerol for the Activation of Calcium-Activated, Phospholipid-Dependent Protein Kinase1

Cited by 179 publications

References 0 publications

Muscarinic Acetylcholine Receptor Regulation of TRP6 Ca2+ Channel Isoforms

Muscarinic Acetylcholine Receptor Regulation of TRP6 Ca2+ Channel Isoforms

Thrombin and activators of protein kinase C modulate secretory responses of permeabilised human platelets induced by Ca²⁺

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

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Specificity of the Fatty Acyl Moieties of Diacylglycerol for the Activation of Calcium-Activated, Phospholipid-Dependent Protein Kinase1

Cited by 179 publications

References 0 publications

Muscarinic Acetylcholine Receptor Regulation of TRP6 Ca2+ Channel Isoforms

Muscarinic Acetylcholine Receptor Regulation of TRP6 Ca2+ Channel Isoforms

Thrombin and activators of protein kinase C modulate secretory responses of permeabilised human platelets induced by Ca2+

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

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Thrombin and activators of protein kinase C modulate secretory responses of permeabilised human platelets induced by Ca²⁺