Characterization of a new liver- and kidney-specific pfkfb3 isozyme that is downregulated by cell proliferation and dedifferentiation.
The bifunctional enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2) catalyzes the synthesis and degradation of fructose 2,6-bisphosphate (Fru-2,6-P(2)), a signalling molecule that controls the balance between glycolysis and gluconeogenesis in several cell types. Four genes, designated Pfkfb1-4, code several PFK-2 isozymes that differ in their kinetic properties, molecular masses, and regulation by protein kinases. In rat tissues, Pfkfb3 gene accounts for eight splice variants and two of them, ubiquitous and inducible PFK-2 isozymes, have been extensively studied and related to cell proliferation and tumour metabolism. Here, we characterize a new kidney- and liver-specific Pfkfb3 isozyme, a product of the RB2K3 splice variant, and demonstrate that its expression, in primary cultured hepatocytes, depends on hepatic cell proliferation and dedifferentiation. In parallel, our results provide further evidence that ubiquitous PFK-2 is a crucial isozyme in supporting growing and proliferant cell metabolism.
Duran
Joan
J
Unitat Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques, Campus de Ciències de la Salut, IDIBELL - Universitat de Barcelona, Spain.
Gómez
Marta
M
Navarro-Sabate
Aurea
A
Riera-Sans
Lluís
L
Obach
Mercè
M
Manzano
Anna
A
Perales
Jose C
JC
Bartrons
Ramon
R
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D022781:Hepatocytes / Q000166:cytology* / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000166:cytology* / Q000201:enzymology*; D008297:Male; D009928:Organ Specificity; D025481:Phosphofructokinase-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D007527:Isoenzymes; C526918:Pfkfb3 protein, rat; D025481:Phosphofructokinase-2