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.
Skip Nav Destination
Article navigation
August 2004
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Review Article|
July 27 2004
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis
Mark H. RIDER;
Mark H. RIDER
1
*Hormone and Metabolic Research Unit, Université Catholique de Louvain and Christian de Duve Institute of Cellular Pathology, 75, Avenue Hippocrate, B-1200 Brussels, Belgium
1To whom correspondence should be addressed (e-mail rider@horm.ucl.ac.be).
Search for other works by this author on:
Luc BERTRAND;
Luc BERTRAND
†Division of Cardiology, Université Catholique de Louvain, 55, Avenue Hippocrate, B-1200 Brussels, Belgium
Search for other works by this author on:
Didier VERTOMMEN;
Didier VERTOMMEN
*Hormone and Metabolic Research Unit, Université Catholique de Louvain and Christian de Duve Institute of Cellular Pathology, 75, Avenue Hippocrate, B-1200 Brussels, Belgium
Search for other works by this author on:
Paul A. MICHELS;
Paul A. MICHELS
‡Research Unit for Tropical Diseases, Université Catholique de Louvain and Christian de Duve Institute of Cellular Pathology, 75, Avenue Hippocrate, B-1200 Brussels, Belgium
Search for other works by this author on:
Guy G. ROUSSEAU;
Guy G. ROUSSEAU
*Hormone and Metabolic Research Unit, Université Catholique de Louvain and Christian de Duve Institute of Cellular Pathology, 75, Avenue Hippocrate, B-1200 Brussels, Belgium
Search for other works by this author on:
Louis HUE
Louis HUE
*Hormone and Metabolic Research Unit, Université Catholique de Louvain and Christian de Duve Institute of Cellular Pathology, 75, Avenue Hippocrate, B-1200 Brussels, Belgium
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 07 2004
Accepted:
June 01 2004
Accepted Manuscript online:
June 01 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2004
Biochem J (2004) 381 (3): 561–579.
Article history
Received:
May 07 2004
Accepted:
June 01 2004
Accepted Manuscript online:
June 01 2004
Citation
Mark H. RIDER, Luc BERTRAND, Didier VERTOMMEN, Paul A. MICHELS, Guy G. ROUSSEAU, Louis HUE; 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis. Biochem J 1 August 2004; 381 (3): 561–579. doi: https://doi.org/10.1042/BJ20040752
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.