Molecular cloning and tissue‐specific expression of mouse kidney 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase

Batra, Ritu Sonia; Brown, Ruth; Brown, Garry K.; Craig, Ian W.

doi:10.1016/0014-5793(96)00878-2

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…The PFKFB‐2 gene encodes the PFK‐2 isoform originally found in the heart [27,28]. Our results indicate that the heart form was expressed at high levels not only in the heart but also in the brain and lungs.…”

Section: Discussionmentioning

confidence: 70%

Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo

Opentanova²,

2003

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When oxygen becomes limiting, cells shift primarily to a glycolytic mode for generation of energy. A key regulator of glycolytic £ux is fructose-2,6-bisphosphate (F-2,6-BP), a potent allosteric regulator of 6-phosphofructo-1-kinase (PFK-1). The levels of F-2,6-BP are maintained by a family of bifunctional enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB or PFK-2), which have both kinase and phosphatase activities. Each member of the enzyme family is characterized by their phosphatase:kinase activity ratio (K:B) and their tissue-speci¢c expression. Previous work demonstrated that one of the PFK-2 isozyme genes, PFKFB-3, was induced by hypoxia through the hypoxia-inducible factor-1 (HIF-1) pathway. In this study we examined the basal and hypoxic expression of three members of this family in di¡erent organs of mice. Our ¢ndings indicate that all four isozymes (PFKFB-1^4) are responsive to hypoxia in vivo. However, their basal level of expression and hypoxia responsiveness varies in the di¡erent organs studied. Particularly, PFKFB-1 is highly expressed in liver, heart and skeletal muscle, with the highest response to hypoxia found in the testis. PFKFB-2 is mainly expressed in the lungs, brain and heart. However, the highest hypoxia responses are found only in liver and testis. PFKFB-3 has a variable low basal level of expression in all organs, except skeletal muscle, where it is highly expressed. Most importantly, its hypoxia responsiveness is the most ample of all three genes, being strongly induced in the lungs, liver, kidney, brain, heart and testis. Further studies showed that PFKFB-1 and PFKFB-2 were highly responsive to hypoxia mimics such as transition metals, iron chelators and inhibitors of HIF hydroxylases, suggesting that the hypoxia responsiveness of these genes is also regulated by HIF proteins. In summary, our data demonstrate that PFK-2 genes are responsive to hypoxia in vivo, indicating a physiological role in the adaptation of the organism to environmental or localized hypoxia/ischemia.

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Section: Discussionmentioning

confidence: 70%

Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo

Opentanova²,

2003

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“…Mammalian PFK-2/FBPase-2 sequences have been derived from cDNAs obtained from liver (rat [60,61], human [62,63], bovine [64] and mouse [65]), skeletal muscle (rat [66]), heart (rat [67], bovine [68], human [23] and mouse [65]), placenta/brain (human [25,69], bovine [24] and rat [70]) and testis (human [16] and rat [11]). Sequences are also available from birds (chicken liver [71]), amphibians (frog muscle and frog liver [72]), fish (seabream, Sparus aurata [73]), plants (Arabidopsis thaliana [74], potato [75] and spinach [76]), baker's yeast [77][78][79] and from various genome projects, such as Caenorhabditis elegans, Drosophila melanogaster, Neurospora crassa, Schizosaccharomyces pombe and trypanosomatids.…”

Section: Evolution Of Pfk-2/fbpase-2mentioning

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

355

358

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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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“…The heart (H) isozyme is encoded by mRNAs that originate from gene B [10]. Other PFK‐2/FBPase isozymes have been studied in testis [11], brain [12], perinatal liver [13], pancreatic islets [14], kidney [15] and placenta [16].…”

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confidence: 99%

Expression and regulation of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐ bisphosphatase isozymes in white adipose tissue

Bruni

Vandoolaeghe

Rousseau

et al. 1999

European Journal of Biochemistry

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The aim of this work was to identify the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) isozyme(s) present in white adipose tissue. Ion-exchange chromatography of PFK-2 from rat epididymal fat pads yielded an elution pattern compatible with the presence of both the L (liver) and M (muscle) isozymes. This was consistent with a study of the phosphorylation of the purified adipose tissue enzyme by cAMP-dependent protein kinase, by specific labelling of the preparation with [2-32 P]fructose 2,6-bisphosphate and by reaction with antibodies. Characterization of the PFK-2/FBPase-2 mRNAs showed that mature adipocytes express the mRNA that codes for the L isozyme and the two mRNAs that code for the M isozyme. Preadipocytes expressed mRNA that codes for the M isozyme. Incubation of rat epididymal fat pads with adrenaline stimulated glycolysis but decreased fructose 2,6-bisphosphate concentrations without significant inactivation of PFK-2. These results support previous findings showing that fructose 2,6-bisphosphate is not involved in the adrenaline-induced stimulation of glycolysis in white adipose tissue.

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Molecular cloning and tissue‐specific expression of mouse kidney 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase

Cited by 7 publications

References 34 publications

Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo

Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo

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

Expression and regulation of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐ bisphosphatase isozymes in white adipose tissue

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Molecular cloning and tissue‐specific expression of mouse kidney 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase

Cited by 7 publications

References 34 publications

Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo

Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo

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

Expression and regulation of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐ bisphosphatase isozymes in white adipose tissue

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Expression and regulation of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐ bisphosphatase isozymes in white adipose tissue