Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of vasopressin and some of its inhibitors on the extent of MT polymerization (assembly) were studied in renal medullary slices by means of temperature-dependent polymerization-depolymerization procedure to determine the relative ratio of free (unpolymerized) tubulin to assembled MT's. Assembled MT's were stabilized in a medium containing high concentrations of glycerol and DMSO. Tubulin was assessed indirectly by the [3H]-CLC-binding assay. Incubation of slices at temperatures higher than 20 degree C promoted MT polymerization. Although vasopressin markedly increased the tissue levels of cAMP and activated in situ cAMP-dependent protein kinase, it did not change the extent of MT polymerization. On the other hand, VBL and to a lesser degree lithium chloride inhibited the rate of MT assembly. This finding suggests that VBL and lithium, which are known to inhibit the antidiuretic effect of vasopressin in vivo, may exert at least part of their inhibitory effect by interfering with MT assembly in the renal medulla. Present results thus are consistent with the view that vasopressin does not influence the extent of cytoplasmic MT polymerization in spite of the increase in tissue cAMP level and activation of protein kinase but that inact MT's are required for the cellular action of vasopressin.
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PMID:Microtubule assembly in renal medullary slices: effects of vasopressin, vinblastine, and lithium. 68 12

We examined alkaline phosphatase (ALP) activity in the HL-60 cell induced by retinoic acid (RA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF induced a small but significant increase of NBT-reducing ability and ALP activity of the HL-60 cells. Among various inducers of cell differentiation, 1,25(OH)2D3 and dimethylsulfoxide (DMSO) caused the increase of the NBT-reducing ability and the suppression of ALP activity induced by rhG-CSF, while RA enhanced both of them. Protein kinase C inhibitors (H-7 and staurosporine) but not a protein kinase A inhibitor (HA1004) significantly suppressed the ALP activity induced by the simultaneous treatment with RA and rhG-CSF.
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PMID:[The effects of retinoic acid and recombinant human granulocyte colony-stimulating factor on alkaline phosphatase activity of HL-60 cells]. 128 12

In vitro erythroid differentiation of mouse erythroleukemia (MEL) cells was induced by combinations of topoisomerase and protein kinase inhibitors. Neither inhibitor alone exhibited inducing activity. Although inhibitors of topoisomerases I and II were equally effective in the synergistic induction of erythroid differentiation, only inhibitors of tyrosine kinases, not of serine/threonine kinases, exhibited synergistic activity. The erythroid differentiation induced by the combination of topoisomerase and protein tyrosine kinase inhibitors was distinguished from that induced by typical erythroid inducing agents such as DMSO or HMBA by (1) earlier hemoglobin accumulation in the cells and (2) insensitivity to specific inhibitors (dexamethasone and sodium orthovanadate) of MEL cell differentiation.
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PMID:Synergistic induction of erythroid differentiation of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases. 131 8

In neutrophils, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the translocation of the Ca(++)- and phospholipid-dependent protein kinase, protein kinase C (PK-C) from the soluble to the particulate fraction. At the same time there was a corresponding increase in the amount of Ca(++)- and phospholipid-independent protein kinase activity recovered in the soluble fraction. This soluble Ca(++)- and phospholipid-independent protein kinase presumably reflects proteolytic activation of the particulate associated PK-C. Bone marrow and undifferentiated HL-60 cells also translocated PK-C to the particulate fraction in response to TPA but did not accumulate the soluble Ca(++)- and phospholipid-independent form of the enzyme. Similar results were obtained using HL-60 cells induced to differentiate with dimethyl sulphoxide (DMSO), recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) or 1 alpha,25-dihydroxyvitamin D3. There was also no significant change in either the number or time of expression of differentiation-specific cell surface antigens observed on HL-60 cells induced to differentiate with either DMSO, 1 alpha,25-dihydroxyvitamin D3 or TPA in the presence of cyclosporin A, an agent reported to inhibit the proteolytic breakdown of PK-C to the Ca(++)- and phospholipid-independent form. Likewise, cyclosporin A did not affect the rate of extent of differentiation of primary bone marrow cell cultures. These results suggest that the proteolytically activated and phospholipid-independent form of PK-C is probably not involved in haemopoietic cell differentiation.
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PMID:Examination of the role of the proteolytically-activated form of protein kinase C in the differentiation of human haemopoietic cells. 142 3

The surface glycoproteins of influenza A viruses are the viral components first recognized by the immune system of the infected host, and they are the viral proteins first to contact the infecting cell. Cleavage of the hemagglutinin (HA) is the presupposition for the uptake and fusion between viral and endosomal membranes at a relatively low pH. If this cleavage does not occur during synthesis and migration within the cell, an external trypsin-like protease has to activate the virus with a non-cleaved HA. This latter property is presumably the reason, why such a large reservoir of non-pathogenic influenza A viruses could be built up in water fowl. Especially feral ducks can disseminate influenza viruses along their flight routes all over the world. The role of the neuraminidase (NA) in the infectious process is not so clear. Its main task in the natural infection seems to be removal of mucoids at the site of entry and in this way to start the primary infection. The synthesis of the viral proteins is a highly regulated process. There is not only a transcriptional but also a translational control. The viral glycoproteins belong to the late proteins. Specifically their synthesis can be inhibited by compounds acting in completely different ways like a specific methylase inhibitor (3DA-Ado), a protein phosphokinase C inhibitor (H7), or a lipid solvent (DMSO). It remains to be determined whether the underlining mechanism is in all these cases the same, namely posttranscriptional modification of viral mRNA. All these viral components do not act separately but they cooperate in their functions and sometimes interfere with each other.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis and function of influenza A virus glycoproteins. 193 Jan 3

HL-60 cells were derived from a patient with myelocytic leukemia, and are known to be in the promyelocytic stage and to differentiate into myelocytes or granulocytes after induction with several materials, e.g., DMSO, retinoic acid, and interferons. The authors intended in this report to determine whether asbestos fibers have any effect on the differentiation processes of HL-60 cells induced with DMSO. The cells were induced to differentiate by incubation with 1.25% DMSO for 4 days. A decrease in the percentage of c-myc-protein-positive cells and an increase in the number of C3bi receptor (CD11b) positive cells were observed after differentiation. When crocidolite (50 micrograms/ml) was added to the culture dishes at the beginning of the experiments, the differentiation was inhibited. An increase in the percentage of c-myc-protein-positive cells and a decrease in that of C3bi-receptor-positive cells were observed compared with the cells induced with DMSO alone. It has been reported that DMSO activates phospholipid- and Ca2(+)-dependent protein kinase and induces the differentiation of HL-60 cells. The mechanisms of inhibition by crocidolite fibers of the effects of DMSO remain to be clarified, but the strength of activation of phospholipid- and Ca2(+)-dependent protein kinase may play an important role in the following induction of cell differentiation.
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PMID:[Suppressive effect of crocidolite fibers on the differentiation of HL-60 cells induced with DMSO]. 216 2

To clarify the role of protein kinase C and protein kinase A in cell proliferation and differentiation, the effects of K252a and its derivatives (K252b, KT5720), which have different inhibitory activity to these protein kinases, on the proliferation and differentiation of HL-60 cells were investigated. The proliferation and DNA synthesis of the HL-60 cells were inhibited by K252a in a dose dependent manner. However, K252b and KT5720 which are more specific inhibitors of protein kinase C or protein kinase A, respectively, had no observable effect on cell proliferation. K252a (40nM) enhanced the differentiation of HL-60 cells induced by 1,25(OH)2D3, retinoic acid and DMSO. K252b and KT5720 did not affect 1,25(OH)2D3-induced differentiation. K252a significantly inhibited the differentiation induced by PMA. These results demonstrate that K252a but not its derivatives can function as an antitumor drug and enhancer of the differentiation induced by various inducers.
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PMID:Induction of differentiation of HL-60 cells by protein kinase C inhibitor, K252a. 239 82

We have previously reported an inhibition of the rat myometrial Na+/K+-ATPase by micromolar Ca2+ concentrations which was abolished by SDS treatment of the microsomal preparation. Application of dimethyl sulphoxide (DMSO) prevented this effect of SDS. In this report, we present our investigation into the mechanism of the inhibitory effect of Ca2+ on the myometrial Na+/K+-ATPase. We observed that, in parallel with inhibition by Ca2+, phosphorylation of a number of membrane components was abolished by SDS treatment of the microsome fraction. Exogenously added calmodulin had no effect. However, the catalytic subunit of cAMP-dependent protein kinase restored Ca2+ sensitivity of the Na+/K+-ATPase and phosphorylation of the other components. Furthermore, addition of the heat-stable protein kinase inhibitor reduced drastically the Ca2+ sensitivity of the Na+/K+-ATPase, as well as the phosphorylation of a number of proteins in the myometrial microsome fraction. It is concluded that the cAMP-dependent protein kinase may be involved in the modulation of Na+/K+-ATPase activity by Ca2+ in the myometrial plasma membrane.
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PMID:Possible regulation of the myometrial Na+/K+-ATPase activity by Ca2+ and cAMP-dependent protein kinase. 283 4

The effects of differentiating agents on the activity and phosphorylation pattern produced by phospholipid- and Ca2+-dependent protein kinase (PL-Ca-PK) were examined in human promyelocytic leukemia cell line HL-60. Dimethyl sulfoxide (DMSO), retinoic acid (RA), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] increased the appearance of mature myelocytic (DMSO and RA) or monocytic [1,25(OH)2D3] cells. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increased the appearance of adherent macrophage-like cells. Coincident with the appearance of differentiated cells induced by DMSO, RA, and 1,25(OH)2D3 was an increase in PL-Ca-PK activity. In contrast, TPA treatment resulted in the rapid disappearance of PL-Ca-PK and the induction of phospholipid- and Ca2+- (PL-Ca-) independent protein kinase activity. The phosphorylation pattern resulting from endogenous PL-Ca-PK in extracts from cells treated with DMSO, RA, or 1,25(OH)2D3 showed a prominent phosphorylated protein of molecular weight 37,000 (pp37) and 38,000 (pp38) which was related to the appearance of the myelocyte/monocyte phenotype. pp37 and pp38 were also present in TPA-treated cells, but their phosphorylation was no longer dependent on the presence of phospholipid and calcium. Cells treated with DMSO and RA also exhibited a PL-Ca-dependent pp21 which was barely evident in 1,25(OH)2D3-treated cells and thus represented a myeloid cell marker. Also present was a prominent PL-Ca-dependent pp19 which remained unchanged following treatment with DMSO, RA, and 1,25(OH)2D3, but which diminished markedly in TPA-treated cells. On the other hand, TPA-treated cells exhibited a characteristic pp130 which was antigenically related to the actin binding protein, vinculin. These results indicate that there are characteristic PL-Ca-dependent phosphorylated proteins indicative of mature myelocytic and monocytic cells, as well as PL-Ca-independent phosphorylated proteins characteristic of the macrophage-like phenotype.
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PMID:Phospholipid- and Ca2+-dependent protein kinase activity and protein phosphorylation patterns in the differentiation of human promyelocytic leukemia cell line HL-60. 316 11

Studies have been carried out to analyze protein phosphorylation in membranes isolated from adriamycin resistant HL60 cells which have been grown for various time periods in the presence of dimethylsulfoxide (DMSO), retinoic acid (RA) or 12-O-tetradecanoylphorbol-13-acetate (TPA). The results show that membranes isolated from cells treated with these agents are defective in the phosphorylation of P150, a membrane phosphoprotein associated with drug resistance in HL60 cells. This response is highly selective since only a few membrane proteins show decreased phosphorylation levels under these conditions. Magnesium dependent protein kinase activity in membranes from cells treated with DMSO, RA or TPA is not altered relative to untreated membranes under conditions where there is a major decrease in P150 phosphorylation. Additional studies also show that treatment of resistant cells with TPA results in a major decrease in the in vivo phosphorylation of P150. These results thus demonstrate that agents capable of inducing differentiation in HL60 cells can selectively modulate the phosphorylation of P150. This system should be of value in clarifying mechanisms involved in the phosphorylation of this protein.
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PMID:Dimethylsulfoxide, retinoic acid and 12-O-tetradecanoylphorbol-13-acetate induce a selective decrease in the phosphorylation of P150, a surface membrane phosphoprotein of HL60 cells resistant to adriamycin. 346 85


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