Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The compound 12-O-tetradecanoylphorbol-13-acetate (TPA) is extremely toxic to the P13 subclone of the Jurkat human T-cell leukemia line. By selecting for growth in the presence of TPA, we have isolated two TPA-resistant variants of these cells, P13-50 and P13-5/A8. Studies of protein kinase C (PKC) enzyme activity, immunoblot analyses, and assays for PKC mRNAs indicate that both of these variants express lower levels of PKC than do the parental P13 cells. We suggest that this protects them from the toxic effects of TPA. The P13-5/A8 cells are of particular interest because not only are they resistant to TPA toxicity but they actually require TPA for optimal growth. These cells have a more profound decrease in PKC expression that do P13-50 cells. In addition, P13-5/A8 cells display very little, if any, surface expression of CD45, a receptor-linked tyrosine protein phosphatase, and lck, a lymphocyte-specific tyrosine kinase. On the other hand, they express a very high level of interleukin-2 receptor. A model is proposed that suggests that these cells are dependent on TPA because they have defects in both the PKC and tyrosine kinase signal transduction pathways, and that TPA compensates for these defects by providing a strong stimulus to the residual level of PKC. This variant may be useful for studying the interactions between tyrosine kinase and PKC pathways in controlling the various functions of T lymphocytes.
...
PMID:Altered expression of protein kinase C, lck, and CD45 in a 12-O-tetradecanoylphorbol-13-acetate-dependent leukemic T-cell variant that expresses a high level of interleukin-2 receptor. 153 Aug 79

Assays of neutrophil phosphotyrosine phosphatase activity and determination of haematological parameters were performed on 12 trisomic 21 probands without any clinical or biological symptom of other evolutive disease. Haematological studies showed the two main classical abnormalities: the existence of a macrocytosis and an enhanced lymphocyte count. Of interest are the very reduced rates of phosphotyrosine phosphatase activity found in granulocytes from these patients. This defect in protein phosphatase can be considered as an additional enzymatic change extending the list of modified factors recognized at molecular and cellular levels in subjects whose risk of leukaemia is significantly increased.
...
PMID:Phosphotyrosine phosphatase activity and haematologic changes in Down's syndrome patients. 153 24

The suppressive effect of glucocorticoids (GC) upon antigen-induced phosphatidylinositol phospholipase C (PI-PLC) activity and inositol phosphate formation by rat basophilic leukemia cells (RBL-2H3) has been characterized. Addition of antigen for a period of 1-30 min enhanced production of [3H]inositol monophosphate (IP1), inositol 1,4-bisphosphate (IP2) and inositol 1,4,5-trisphosphate (IP3) by about 5-10-fold. Pretreatment with hydrocortisone (HC) reduced formation of the various inositol phosphates (IPs) and degradation of phosphatidylinositol 4,5-bisphosphate (PIP2) by an average of 50%. Maximal inhibition of hydrolysis of PIP2 and reduction in stimulation of IP3 formation was reached after 4 h of preincubation with 2.10(-6) M of HC. Cycloheximide and RU486, a GC receptor antagonist, completely prevented the inhibitory effect of HC on IP formation. Other GC, dexamethasone (DEX) and triamcinolone (each at 2.10(-7) M) markedly suppressed antigen induced IP3 production, while aldosterone and sex steroids such as estradiol and progesterone (each at 2.10(-6) M) were virtually inactive. Antigen-stimulated phosphorylation of a 18 kDa and other proteins was inhibited by about 60% following pretreatment with the GC. This inhibition was in turn prevented by cycloheximide. DEX also doubled the activity of cellular acid phosphatase activity. The results suggest that the inhibitory effect of GC is specific, receptor-mediated, dependent on protein synthesis and possibly mediated by protein phosphatase activity.
...
PMID:Characterization of glucocorticoid inhibition of antigen-induced inositolphosphate formation by rat basophilic leukemia cells: possible involvement of phosphatases. 166 Nov 66

The suppressive effect of glucocorticoids (GC) upon antigen-induced phosphatidylinositol phospholipase C (PI-PLC) activity and inositol phosphate formation by rat basophilic leukemia cells (RBL-2H3) has been characterized. Addition of antigen for a period of 1-30 min enhanced production of [3H]inositol monophosphate (IP1), inositol 1,4-biphosphate (IP2) and inositol 1,4,5-triphosphate (IP3) by about 5-10 fold. Pretreatment with hydrocortisone (HC) and dexamethasone (DEX) reduced formation of the various inositol phosphates (IPs) and degradation of phosphatidylinositol-4-5-biphosphate (PIP2) by an average of 50% Antigen-stimulated phosphorylation of an 18 kDA and other proteins was inhibited by about 60% following pretreatment with the GC. This inhibition was in turn prevented by cycloheximide. Moreover, DEX doubled cellular acid phosphatase activity. The results suggest that the inhibitory effect of GC is possibly mediated, among other things, by protein phosphatase activity.
...
PMID:Glucocorticoid inhibition of antigen-induced inositol phosphate formation: possible involvement of phosphatases. 166 8

Human promyelocytic leukemia cell line, HL-60, undergoes macrophagic differentiation when it is stimulated with TPA (12-O-tetradecanoylphorbol-13-acetate). We have cloned ETR101 cDNA whose mRNA was induced immediate early (30 min) and transiently by TPA. The mRNA is superinduced by addition of the protein synthesis inhibitor cycloheximide. The sequence of ETR101 cDNA (1826 base pairs) reveals that (i) it will encode a protein of 223 amino acids with a formula molecular weight of 24,200, (ii) the amino acid sequence is highly homologous to mouse chx1 protein whose mRNA was found recently to be enhanced in activated T lymphocytes in response to cycloheximide, (iii) the amino acid sequence is also weakly homologous to jun family gene products, and (iv) in the mRNA 3'-flanking region, there is a unique GUUUG sequence which is complementary to a part of B1 repetitive sequence and may be involved in mRNA degradation. ETR101 mRNA is induced by TPA in a wide variety of leukemia cells including myeloid, T-lymphoid, and B-lymphoid lineages. We have found that this mRNA is also induced by okadaic acid, a protein phosphatase inhibitor, and that TPA or cycloheximide act synergistically with okadaic acid. In addition, the induction is inhibited by protein kinase C inhibitors. Therefore, ETR101 mRNA level is controlled, either directly or indirectly, by protein phosphorylation.
...
PMID:Expression of a novel immediate early gene during 12-O-tetradecanoylphorbol-13-acetate-induced macrophagic differentiation of HL-60 cells. 206 3

The long terminal repeat (LTR) of the human T-cell leukemia virus type I (HTLV-I) contains an imperfect repeat of 21 nucleotides which governs the response to the virus trans-activator protein tax and to cyclic AMP. In a murine thymocyte cell line defective in the catalytic subunit of protein kinase A, the response of the HTLV-I LTR to cyclic AMP is abolished and the response to tax is substantially diminished. This report shows that a factor present in nuclear extracts of wild-type cells binds to the HTLV-I 21-nucleotide sequence and that this binding activity is missing from the extracts of protein kinase A-defective cells. Treatment of nuclear extracts of protein kinase A-defective cells with the bovine protein kinase A catalytic subunit restores the binding activity, whereas treatment of wild-type nuclear extracts with a protein phosphatase destroys the binding activity. The binding factor is referred to as protein kinase A-dependent factor (PKAF). These results indicate that in murine thymocytes the response of the HTLV-I LTR to cyclic AMP depends upon the binding of a phosphorylated protein to the 21-nucleotide repeat sequence and that the response to tax is partially dependent upon binding of the phosphorylated protein. The results suggest a model in which the phosphorylation of a transcription factor by protein kinase A regulates HTLV-I gene expression.
...
PMID:Protein kinase A-dependent binding of a nuclear factor to the 21-base-pair repeat of the human T-cell leukemia virus type I long terminal repeat. 230 43

Phosphorylation of ribosomal protein S6 in NIH 3T3 fibroblasts is dependent on the presence of serum, but after transformation of these cells by Abelson murine leukemia virus (Ab-MuLV), S6 remained highly phosphorylated on serine residues either in the absence or the presence of serum. To investigate whether S6 phosphorylation in this system was a consequence of the action of the Ab-MuLV tyrosine-specific protein kinase, purified Ab-MuLV kinase made in Escherichia coli was microinjected into Xenopus oocytes and was observed to cause a 7- to 15-fold increase in the phosphorylation of S6 on serine residues. Two-dimensional phosphopeptide maps of S6 phosphorylated in Ab-MuLV-transformed NIH cells in the absence of serum were identical to those of S6 isolated from normal cells grown in the presence of serum. In addition, S6 from oocytes injected with Ab-MuLV kinase yielded an S6 phosphopeptide map indistinguishable from that of serum-stimulated NIH 3T3 cells, whereas S6 from control oocytes lacked several phosphopeptides. Ab-MuLV kinase did not phosphorylate S6 directly in vitro, and microinjection of a mutant Ab-MuLV protein lacking kinase activity had no effect. These results indicate that the Ab-MuLV kinase interacts with a cellular pathway to enhance S6 phosphorylation by directly or indirectly activating an S6 protein kinase and/or inactivating an S6 protein phosphatase.
...
PMID:Phosphorylation of ribosomal protein S6 on serine after microinjection of the Abelson murine leukemia virus tyrosine-specific protein kinase into Xenopus oocytes. 391 7

Cantharidin is a natural toxin that inhibits protein phosphatase type 2A (PP2A) and has antitumour effects in man. We have studied the synthetic analogue, norcantharidin (NCTD), which has less nephrotoxic and phlogogenic side-effects, investigating the effects on the normal haemopoietic system and leukaemia cell growth. Daily intraperitoneal (i.p.) injection of NCTD induced dose and circadian time-dependent transient leucocytosis in normal mice, but did not accelerate bone marrow (BM) regeneration, or have haemopoietic offe-effects following chronic administration. NCTD stimulated the cell cycle progression of granulocyte-macrophage colony-forming cells (GM-CFC), stimulated DNA synthesis and increased the frequency of mitotic cells in short-term human BM cultures. NCTD also stimulated the production of interleukin (IL)-1 beta, colony stimulating activity (CSA) and tumour necrosis factor (TNF)-alpha. Continuous in vitro NCTD treatment, however, inhibited both DNA synthesis and GM-CFC growth. Fluorescence-activated cell sorting (FACS) analysis of DNA profiles and cytological studies in HL-60, K-562 or MRC5V2 (fibroblast) cells indicated that low doses of NCTD accelerated the G1/S phase transition, while higher doses or prolonged incubations inhibited the cell cycle at the G2/M phases or during the formation of postmitotic daughter cells. Electron microscopy revealed that NCTD impaired the neogenesis of chromatin material and nuclear membrane during the M/G1 phase transition in K-562 cells. The biphasic effect of NCTD may be due to inhibition of PP2A activity, which regulates the cell cycle, both at the restriction point and at the G2 and M phases. Our data provide new insight into the cellular and molecular actions of NCTD, and partly explain its therapeutical effects in cancer patients.
...
PMID:Effects of norcantharidin, a protein phosphatase type-2A inhibitor, on the growth of normal and malignant haemopoietic cells. 764 29

Complementary DNA encoding three catalytic subunits of protein phosphatase 1 (PP1 alpha, PP1 beta, and PP1 gamma) and the insulin-stimulated protein kinase 1 (ISPK-1) was analyzed for variations in the coding regions related to insulin-resistant glycogen synthesis in skeletal muscle of 30 patients with non-insulin-dependent diabetes mellitus (NIDDM). The human ISPK-1 cDNA was cloned from T-cell leukemia and placental cDNA libraries and mapped to the short arm of the human X chromosome. Single-strand conformation polymorphism (SSCP) analysis identified a total of six variations in the coding regions of the PP1 genes: two in PP1 alpha at codons 90 and 255; one in PP1 beta at codon 67; and three in PP1 gamma at codons 11,269, and 273, respectively. All were, however, silent single nucleotide substitutions. SSCP analysis of the ISPK-1 gene identified one silent polymorphism at codon 266 and one amino acid variant at codon 38 (Ile-->Ser). This variant was primarily found in one male NIDDM patient. This subject, however, did not exhibit an impairment of muscle insulin-stimulated glycogen synthase activation. No significant differences were found in mRNA levels in muscle of the four genes between 15 NIDDM patients and 14 healthy subjects. Our findings suggest that 1) genetic abnormalities in the coding regions of PP1 alpha, PP1 beta, PP1 gamma, and ISPK-1 are unlikely to be frequently occurring causes of the reduced insulin-stimulated activation of the glycogen synthesis in muscle from the analyzed group of NIDDM patients; 2) the mRNA levels of PP1 alpha, PP1 beta, PP1 gamma, and ISPK-1 are normal in muscle from the NIDDM patients; and 3) putative inherited defects in insulin-stimulated activation of muscle glycogen synthesis in patients with insulin-resistant NIDDM may be located further upstream of ISPK-1 in the insulin action cascade.
...
PMID:Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients. 781 20

Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have previously been reported to induce rapid phosphorylation of the mitogen-activated protein (MAP) kinase. However, little is known about signaling events initiated by both hematopoietins that occur downstream of the MAP kinase. MAP kinase has been shown to phosphorylate the AP-1 transcription factor and also to activate two kinases designated insulin-stimulated protein kinase-1 and MAP kinase-activated protein (MAP-KAP) kinase 2. We show here that IL-3 and GM-CSF induce MAPKAP kinase 2 activity in the human megakaryoblastic leukemia cell line MO7 and phosphorylate the human small heat shock protein Hsp 27 on serine residues in vitro. GM-CSF also induced Hsp 27 phosphorylation in neutrophils in a range similar to that observed in MO7 cells, suggesting that MAPKAP kinase 2-mediated Hsp 27 activation occurs independently of proliferation. Hsp 27 phosphorylation was dose-dependent, occurred as early as 5 minutes after factor exposure, and was inhibited by the tyrosine kinase inhibitors genistein and herbimycin A. Furthermore, the protein phosphatase A2 abolished IL-3- and GM-CSF-induced serine phosphorylation of Hsp 27. Taken together, our findings indicate that tyrosine phosphorylation of MAP kinase is a prerequisite for serine phosphorylation of Hsp 27, which is mediated by MAPKAP kinase 2. Hsp 27 has shown activation-dependent translocation from the cytosolic to the nuclear region and has been linked to the cellular stress response. However, its precise function is largely unknown. Our data identify Hsp 27 as a target of the IL-3/GM-CSF stimulation pathway that involves MAP kinase and MAPKAP kinase 2. In addition, our results indicate that Hsp 27 may be target of phosphorylation events not only in the stress response but also in unstressed cells responding to cytokine stimulation.
...
PMID:Interleukin-3 and granulocyte-macrophage colony-stimulating factor induce activation of the MAPKAP kinase 2 resulting in in vitro serine phosphorylation of the small heat shock protein (Hsp 27). 1101 49


1 2 3 4 5 6 Next >>

---