Effect of TPA on fructose 2,6-bisphosphate levels and protein kinase C activity in B-chronic lymphocytic leukemia (B-CLL)

Colomer, Dolors; Corrons, J.L.L. Vives; Bartrons, Ramón

doi:10.1016/0925-4439(91)90080-s

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…Therefore pp60 v-src, acting via PKC, could change the isoenzyme expression of PFK-2/FBPase-2 [194]. Phorbol esters increase Fru-2,6-P 2 concentrations in chick embryo fibroblasts [195], in human fibroblasts [196], in human platelets [197], in differentiating megakaryocytes [198], in human B-lymphocytes [199], in mouse spleen lymphocytes and purified B-cells [190], and in foetal rat hepatocytes [200]. The effect of phorbol esters to increase Fru-2,6-P 2 in these systems could be attributed to a rise in hexose 6-phosphates and in some cases to PFK-2 activation.…”

Section: Vertommen L Bertrand L Hue and M H Rider Unpublishmentioning

confidence: 99%

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis

Rider

Bertrand

Vertommen

et al. 2004

Biochemical Journal

357

350

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Fru-2,6-P2 (fructose 2,6-bisphosphate) is a signal molecule that controls glycolysis. Since its discovery more than 20 years ago, inroads have been made towards the understanding of the structure-function relationships in PFK-2 (6-phosphofructo-2-kinase)/FBPase-2 (fructose-2,6-bisphosphatase), the homodimeric bifunctional enzyme that catalyses the synthesis and degradation of Fru-2,6-P2. The FBPase-2 domain of the enzyme subunit bears sequence, mechanistic and structural similarity to the histidine phosphatase family of enzymes. The PFK-2 domain was originally thought to resemble bacterial PFK-1 (6-phosphofructo-1-kinase), but this proved not to be correct. Molecular modelling of the PFK-2 domain revealed that, instead, it has the same fold as adenylate kinase. This was confirmed by X-ray crystallography. A PFK-2/FBPase-2 sequence in the genome of one prokaryote, the proteobacterium Desulfovibrio desulfuricans, could be the result of horizontal gene transfer from a eukaryote distantly related to all other organisms, possibly a protist. This, together with the presence of PFK-2/FBPase-2 genes in trypanosomatids (albeit with possibly only one of the domains active), indicates that fusion of genes initially coding for separate PFK-2 and FBPase-2 domains might have occurred early in evolution. In the enzyme homodimer, the PFK-2 domains come together in a head-to-head like fashion, whereas the FBPase-2 domains can function as monomers. There are four PFK-2/FBPase-2 isoenzymes in mammals, each coded by a different gene that expresses several isoforms of each isoenzyme. In these genes, regulatory sequences have been identified which account for their long-term control by hormones and tissue-specific transcription factors. One of these, HNF-6 (hepatocyte nuclear factor-6), was discovered in this way. As to short-term control, the liver isoenzyme is phosphorylated at the N-terminus, adjacent to the PFK-2 domain, by PKA (cAMP-dependent protein kinase), leading to PFK-2 inactivation and FBPase-2 activation. In contrast, the heart isoenzyme is phosphorylated at the C-terminus by several protein kinases in different signalling pathways, resulting in PFK-2 activation.

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Section: Vertommen L Bertrand L Hue and M H Rider Unpublishmentioning

confidence: 99%

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis

Rider

Bertrand

Vertommen

et al. 2004

Biochemical Journal

357

350

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“…An increase in Fru‐2,6‐P 2 concentration in growing cells activates glycolysis and correlates with an enhancement of PFK‐2/FBPase‐2 expression and activity [4–8]. Transformation of chick embryo fibroblasts by retrovirus carrying either the v‐src or v‐fps oncogene induced Fru‐2,6‐P 2 synthesis and increased glycolytic flux and cell proliferation [5].…”

Section: Introductionmentioning

confidence: 99%

Cells overexpressing fructose‐2,6‐bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stress

et al. 2000

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Changes in the content of fructose-2,6-bisphosphate, a modulator of glycolytic flux, also affect other metabolic fluxes such as the non-oxidative pentose phosphate pathway. Since this is the main source of precursors for biosynthesis in proliferating cells, PFK-2/FBPase-2 has been proposed as a potential target for neoplastic treatments. Here we provide evidence that cells with a low content of fructose-2,6-bisphosphate have a lower energy status than controls, but they are also less sensitive to oxidative stress. This feature is related to the activation of the oxidative branch of the pentose phosphate pathway and the increased production of NADPH. ß

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“…23 Briefly, cells were lysed in 20 mM Tris (tris-hydroxymethyl-aminomethane)-HCl, pH 7.5; 0.3 M saccharose; 2 mM EGTA (ethylene glycol-bis-(b-amioethylether) N,N,N 0 ,N 0 -tetraacetic acid); 2 mM EDTA (ethylenediaminetetraacetic acid); 10 mM 2-mercapto-ethanol; 1 mM PMSF; 0.01 mg/ml leupeptin; 0.5% aprotinin; 1% Nonidet P-40. After sonication three times for 10 s, cells were centrifuged at 14 000 rpm for 30 min at 41C.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells

et al. 2004

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Fludarabine is considered the treatment of choice for most patients with chronic lymphocytic leukemia (CLL). We have analyzed the role of plasma membrane transporters in nucleoside-derived drug bioavailability and action in CLL cells. Among the known plasma membrane transporters, we have previously observed a significant correlation between fludarabine uptake via ENT carriers and ex vivo sensitivity of CLL cells to fludarabine, although mRNA amounts of the equilibrative nucleoside transporters hENT1 and hENT2 do not show any predictive response to treatment. In this study, using polyclonal monospecific antibodies we have observed a significant correlation between the expression of hENT2 by Western blot and fludarabine uptake via hENT carriers and also with ex vivo sensitivity of CLL cells to fludarabine. These results suggest that the equilibrative nucleoside transporter hENT2 plays a role in fludarabine responsiveness in CLL patients.

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Effect of TPA on fructose 2,6-bisphosphate levels and protein kinase C activity in B-chronic lymphocytic leukemia (B-CLL)

Cited by 9 publications

References 27 publications

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis

Cells overexpressing fructose‐2,6‐bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stress

Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells

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