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Biomedical subjects

K Kaibuchi

Publications and source records attributed to K Kaibuchi.

232 records · Page 13Linked to original sources
PubMed1984

Protein phosphorylation and mechanism of action of tumor-promoting phorbol esters.

The phorbol ester TPA may be intercalated into the membrane phospholipid bilayer and selectively binds to every molecule of C-kinase in exhibiting its full enzymatic activity. Available evidence suggests that C-kinase is the receptive protein of this tumor promoter, and the results presented seem to provide clues for clarifying the mechanism of controlling cell growth and differentiation.

Animals↗
PubMed1983

Elevation of cytoplasmic free calcium concentration by stable thromboxane A2 analogue in human platelets.

9, 11-Epithio-11, 12-methano-thromboxane A2 (STA2), a stable analogue of thromboxane A2, caused a rapid rise in cytoplasmic free Ca2+ concentration ([Ca2+]i) in human platelets as measured with the fluorescent Ca2+ indicator quin2. Concomitantly, this compound induced phosphorylation of myosin light chain which is catalyzed by Ca2+, calmodulin-dependent protein kinase. These reactions were fast enough to trigger serotonin release. 13-Azaprostanoic acid, a receptor level antagonist of thromboxane A2 inhibited STA2-induced elevation of [Ca2+]i, phosphorylation of myosin light chain and serotonin release. These results provide evidence that STA2 interacts with a thromboxane A2 receptor which leads to elevation of [Ca2+]i.

Blood Platelets↗
PubMed1983

A possible role of protein kinase C in signal-induced lysosomal enzyme release.

In platelets, activation of protein kinase C and mobilization of Ca2+ were selectively induced by the addition of 1-oleoyl-2-acetyl-glycerol and a low concentration of A23187, respectively (Kaibuchi, K., Takai, Y., Sawamura, M., Hoshijima, M., Fujikura, T. and Nishizuka, Y. (1983) J. Biol. Chem. 258, 6701-6704). Using this procedure evidence was obtained suggesting that the protein phosphorylation and Ca2+ mobilization were both essential and synergistically effective to cause release of lysosomal acid hydrolases such as N-acetylglucosaminidase. A similar observation was made for the lysosomal enzyme release from rat neutrophils.

Animals↗
PubMed1983

Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation.

When human platelets were stimulated by synthetic diacylglycerol such as 1-oleoyl-2-acetyl-glycerol, which was a potent activator in vitro of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) (Mori, T., Takai, Y., Yu, B., Takahashi, J., Nishizuka, Y., and Fujikura, T. (1982) J. Biochem. (Tokyo) 91, 427-431), a protein having Mr approximately 40,000 (40-kilodalton protein) was rapidly phosphorylated, just as it was by natural extracellular messengers such as thrombin. Fingerprint analysis appeared to indicate that protein kinase C was indeed responsible for this 40-kilodalton protein phosphorylation in intact platelets. Under these conditions, neither inositol phospholipid breakdown nor endogenous diacylglycerol formation was observed, indicating that the synthetic diacylglycerol intercalated into the membrane and directly activated protein kinase C without interaction with cell surface receptors. During this process, the diacylglycerol was converted in situ to the corresponding phosphatidate, 1-oleoyl-2-acetyl-glyceryl-3-phosphoric acid. Experiments with the synthetic diacylglycerol and Ca2+ ionophore A23187 suggested that the protein phosphorylation catalyzed by protein kinase C was a prerequisite requirement for the release of serotonin, and that the receptor-linked protein phosphorylation and Ca2+ mobilization acted synergistically to elicit the full physiological cellular response.

Anti-Bacterial Agents↗
PubMed1983

Synergistic functions of phorbol ester and calcium in serotonin release from human platelets.

In human platelets, thrombin activates Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) and mobilizes Ca2+ concomitantly, whereas 12-O-tetradecanoylphorbol-13-acetate (TPA) may be intercalated into membranes and directly activates protein kinase C without mobilization of Ca2+ in sufficient quantities. A series of experiments with TPA and Ca2+-ionophore (A23187) indicates that activation of protein kinase C is a prerequisite requirement for release of serotonin, and that this enzyme activation and Ca2+ mobilization act synergistically to elicit a full cellular response. Both cyclic AMP and cyclic GMP inhibit activation of protein kinase C by prohibiting the signal-dependent breakdown of inositol phospholipid to produce diacyl-glycerol, but none of these cyclic nucleotides prevents the TPA-induced activation of this enzyme.

Blood Platelets↗
PubMed1982

Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.

Tumor-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) directly activate in vitro Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), which normally requires unsaturated diacylglycerol. Kinetic analysis indicates that TPA can substitute for diacylglycerol and greatly increases the affinity of the enzyme for Ca2+ as well as for phospholipid. Under physiological conditions, the activation of this enzyme appears to be linked to the receptor-mediated phosphatidylinositol breakdown which may be provoked by a wide variety of extracellular messengers, eventually leading to the activation of specific cellular functions or proliferation. Using human platelets as a model system, TPA is shown to enhance the protein kinase C-specific phosphorylation associated with the release reaction in the total absence of phosphatidylinositol breakdown. Various phorbol derivatives which have been shown to be active in tumor promotion are also capable of activating this protein kinase in in vitro systems.

Animals↗
PubMed1982

Phosphatidylinositol turnover in platelet activation; calcium mobilization and protein phosphorylation.

Ca2+-activated, phospholipid-dependent protein kinase (C-kinase) in platelets is normally activated by diacylglycerol, which is derived from phosphatidylinositol through its receptor-linked breakdown. Under appropriate conditions this enzyme can also be activated by synthetic diacylglycerol which is directly added to intact platelets. C-Kinase thus activated preferentially phosphorylates an endogenous platelet protein having a molecular weight of approximately 40,000. This protein phosphorylation is merely a prerequisite but not a sufficient requirement for the release of serotonin. Evidence is presented suggesting that Ca2+ mobilization and C-kinase activation are synergistically involved in the physiological response of platelets to extracellular messengers, such as thrombin, collagen and platelet-activating factor.

Blood Platelets↗
PubMed1982

Counteraction of calcium-activated, phospholipid-dependent protein kinase activation by adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in platelets.

In intact human platelets activated by thrombin, diacylglycerol is produced with the concomitant disappearance of phosphatidylinositol (PI). This reaction is associated with phosphorylation of a protein having a molecular weight of about 40,000 (40 K protein) and serotonin release. All the reactions are inhibited in a parallel manner by incubation of platelets with either dibutyryl cyclic AMP or 8-bromocyclic GMP, prior to the stimulation by thrombin. The inhibition of these reactions is inversely related to phosphorylation of another group of platelet proteins. Since Ca2+-activated, phospholipid-dependent protein kinase (C-Kinase) is activated by diacylglycerol and is responsible for 40 K protein phosphorylation (Kawahara, Y., Takai, Y., Minakuchi, R., Sano, K., & Nishizuka, Y. (1980) Biochem. Biophys. Res. Commun. 97, 309-317), the results suggest that in platelets both cyclic AMP and cyclic GMP may serve as inhibitors of C-Kinase by counteracting the receptor-linked PI breakdown probably through the actions of cyclic nucleotide-dependent protein kinases.

Alprostadil↗
PubMed1981

Cooperative roles of various membrane phospholipids in the activation of calcium-activated, phospholipid-dependent protein kinase.

Although phosphatidylserine is the sole phospholipid effective for the activation of Ca2+-activated, phospholipid-dependent protein kinase in the presence of a small amount of unsaturated diacylglycerol and micromolar concentrations of Ca2+ (Takai, Y., Kishimoto, A., Kikkawa, U., Mori, T., and Nishizuka, Y. (1979) Biochem. Biophys. Res. Commun. 91, 1218-1224), other species of phospholipids modulate the activation of enzyme considerably. When phosphatidylserine is supplemented with phosphatidylethanolamine, further enhancement of the enzymatic activity is observed. Inversely, the addition of phosphatidylcholine or sphingomyelin markedly diminishes the enzyme activation by phosphatidylserine. Phosphatidylinositol, which serves as the source of unsaturated diacylglycerol, and phosphatidic acid do not show significant effects. Kinetic analysis has indicated that phosphatidylethanolamine enhances the enzyme activation by marked increase in the affinity of enzyme for Ca2+ and also by slight increase in the affinity for phosphatidylserine as well as for unsaturated diacylglycerol without affecting the maximum reaction velocity. Phosphatidylcholine and sphingomyelin diminish the enzyme activation in an uncompetitive manner with respect to Ca2+ and in a competitive manner with respect to both phosphatidylserine and unsaturated diacylglycerol. These results suggest that each species of the various membrane phospholipids plays a specific role with positive or negative cooperativity in the activation of this unique protein kinase.

Animals↗