User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades

Primary tabs

Deprez, J Vertommen, Didier [UCL] Alessi, Dario R. Hue, Louis [UCL] Rider, Mark H. [UCL]

To understand the insulin-induced activation of 6-phosphofructo-2-kinase (PFK-2) of the bifunctional enzyme PFK-2/fructose-2,6-bisphosphatase in heart, the effect of phosphorylation by protein kinases of the insulin signaling pathways on PFK-2 activity was studied. Purified PFK-2/fructose-2, 6-bisphosphatase from bovine heart is a mixture of two isoforms (Mr 58,000 and 54,000 on SDS-polyacrylamide gels). The Mr 54,000 protein is an alternatively spliced form, lacking phosphorylation sites for protein kinases. Recombinant enzymes corresponding to the Mr 58,000 (BH1) and Mr 54,000 (BH3) forms were expressed and used as substrates for phosphorylation. The recombinant BH1 isoform was phosphorylated by p70 ribosomal S6 kinase (p70(s6k)), mitogen-activated protein kinase-activated protein kinase-1, and protein kinase B (PKB), whereas the recombinant BH3 isoform was a poor substrate for these protein kinases. Treatment with all protein kinases activated PFK-2 in the recombinant BH1 preparation. Phosphorylation of the recombinant BH1 isoform correlated with PFK-2 activation and was reversed by treatment with protein phosphatase 2A. All the protein kinases phosphorylated Ser-466 and Ser-483 in the BH1 isoform, but to different extents: p70(s6k) preferentially phosphorylated Ser-466, whereas mitogen-activated protein kinase-activated protein kinase-1 and PKB phosphorylated Ser-466 and Ser-483 to a similar extent. We propose that PKB is part of the insulin signaling cascade for PFK-2 activation in heart.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 1997
Journal information "Journal of Biological Chemistry" - Vol. 272, no. 28, p. 17269-17275 (1997)
Peer reviewed yes
Publisher American Society for Biochemistry and Molecular Biology, Inc.
issn 0021-9258
e-issn 1083-351X
Publication status Publié
Affiliation UCL - MD/BICL - Département de biochimie et de biologie cellulaire
MESH Subject Adenosine Triphosphate - metabolism ; Animals ; Cattle ; Chromatography, High Pressure Liquid ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Enzyme Activation ; Insulin - physiology ; Isoenzymes - isolation & purification - metabolism ; Kinetics ; Molecular Weight ; Myocardium - enzymology ; Phosphofructokinase-2 ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor) - metabolism ; Protein Kinases - metabolism ; Protein-Serine-Threonine Kinases - metabolism ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-akt ; Recombinant Proteins - isolation & purification - metabolism ; Ribosomal Protein S6 Kinases ; Ribosomal Protein S6 Kinases, 90-kDa ; Signal Transduction
Links
  1. Hue L, Rider M H, Role of fructose 2,6-bisphosphate in the control of glycolysis in mammalian tissues, 10.1042/bj2450313
  2. COFFER Paul J., WOODGETT James R., Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families, 10.1111/j.1432-1033.1991.tb16305.x
  3. Belacossa, Science, 254, 244 (1991)
  4. Jones P. F., Jakubowicz T., Pitossi F. J., Maurer F., Hemmings B. A., Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily., 10.1073/pnas.88.10.4171
  5. Hue L. Rider M. H. Rousseau G. G. (1990) in Fructose 2,6-Bisphosphate, ed Pilkis S. J. (CRC Press, Inc. Boca Raton, FL), pp 173–192.
  6. Darville Martine I., Chikri Mohamed, Lebeau Etienne, Hue Louis, Rousseau Guy G., A rat gene encoding heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, 10.1016/0014-5793(91)81009-w
  7. Rider M H, Vandamme J, Lebeau E, Vertommen D, Vidal H, Rousseau G G, Vandekerckhove J, Hue L, The two forms of bovine heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase result from alternative splicing, 10.1042/bj2850405
  8. Sakata Junichiro, Uyeda Kosaku, Characterization of two isozymic forms of heart fructose 6-phosphate, 2-kinase:fructose 2,6-bisphosphatase, 10.1016/s0006-291x(05)81088-5
  9. Rider Mark H., Van Damme Josef, Vertommen Didier, Michel Alain, Vandekerckhove Joël, Hue Louis, Evidence for new phosphorylation sites for protein kinase C and cyclic AMP-dependent protein kinase in bovine heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, 10.1016/0014-5793(92)81315-d
  10. Vidal Hubert, Crepin Karine M., Rider Mark H., Hue Louis, Rousseau Guy G., Cloning and expression of novel isoforms of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from bovine heart, 10.1016/0014-5793(93)80898-5
  11. Chikri Mohamed, Rousseau Guy G., Rat gene coding for heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: characterization of an unusual promoter region and identification of four mRNAs, 10.1021/bi00027a040
  12. Hue, J. Biol. Chem., 257, 4308 (1982)
  13. SUTHERLAND Calum, CAMPBELL David G., COHEN Philip, Identification of insulin-stimulated protein kinase-1 as the rabbit equivalent of rskmo-2. Identification of two threonines phosphorylated during activation by mitogen-activated protein kinase, 10.1111/j.1432-1033.1993.tb17696.x
  14. Leighton Ian A., Dalby Kevin N., Barry Caudwell F., Cohen Patricia T.W., Cohen Philip, Comparison of the specificities of p70 S6 kinase and MAPKAP kinase-1 identifies a relatively specific substrate for p70 S6 kinase: the N-terminal kinase domain of MAPKAP kinase-1 is essential for peptide phosphorylation, 10.1016/0014-5793(95)01170-j
  15. Alessi Dario R., James Stephen R., Downes C.Peter, Holmes Andrew B., Gaffney Piers R.J., Reese Colin B., Cohen Philip, Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα, 10.1016/s0960-9822(06)00122-9
  16. Reimann Erwin M., Beham Richard A., [6] Catalytic subunit of cAMP-dependent protein kinase, Methods in Enzymology (1983) ISBN:9780121819996 p.51-55, 10.1016/0076-6879(83)99039-0
  17. Cohen Philip, Alemany Susana, Therese Brian A., Resink J., Stralfors Peter, Lim Tung H.Y., [37] Protein phosphatase-1 and protein phosphatase-2A from rabbit skeletal muscle, Methods in Enzymology (1988) ISBN:9780121820602 p.390-408, 10.1016/0076-6879(88)59039-0
  18. Scott J. D., Glaccum M. B., Fischer E. H., Krebs E. G., Primary-structure requirements for inhibition by the heat-stable inhibitor of the cAMP-dependent protein kinase., 10.1073/pnas.83.6.1613
  19. Vertommen Didier, Bertrand Luc, Sontag Bruno, Di Pietro Attilio, Louckx Marc P., Vidal Hubert, Hue Louis, Rider Mark H., The ATP-binding Site in the 2-Kinase Domain of Liver 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase : STUDY OF THE ROLE OF Lys-54 AND Thr-55 BY SITE-DIRECTED MUTAGENESIS, 10.1074/jbc.271.30.17875
  20. LAEMMLI U. K., Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4, 10.1038/227680a0
  21. Roskoski Robert, [1] Assays of protein kinase, Methods in Enzymology (1983) ISBN:9780121819996 p.3-6, 10.1016/0076-6879(83)99034-1
  22. Crepin, J. Biol. Chem., 268, 15277 (1993)
  23. Rider Mark H., Hue Louis, Activation of rat heart phosphofructokinase-2 by insulin in vivo, 10.1016/0014-5793(84)81223-5
  24. Price, J. Biol. Chem., 264, 13825 (1989)
  25. Cross Darren A. E., Alessi Dario R., Cohen Philip, Andjelkovich Mirjana, Hemmings Brian A., Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B, 10.1038/378785a0
  26. Stokoe, EMBO J., 11, 3985 (1992)
  27. Bradford Marion M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, 10.1016/0003-2697(76)90527-3
  28. Allen G. (1989) in Sequencing of Proteins and Peptides, eds Work T. S. Burdon R. H. (Elsevier Science Publishers B. V. Amsterdam), pp 140–141.
  29. Abe Yumiko, Minami Yoshiko, Li Yang, Nguyen Cu, Uyeda Kosaku, Expression of Bovine Heart Fructose 6-Phosphate,2-kinase:Fructose 2,6-Bisphosphatase and Determination of the Role of the Carboxyl Terminus by Mutagenesis, 10.1021/bi00008a020
  30. Gevaert K. Rider M. Puype M. Van Damme J. De Boeck S. Vandekerckhove J. (1995) in Methods in Protein Structure Analysis, eds Atassi M. Z. Appella E. (Plenum Press, New York), pp 15–26.
  31. Kitamura, J. Biol. Chem., 263, 16796 (1988)
  32. Rider M H, Hue L, Phosphorylation of purified bovine heart and rat liver 6-phosphofructo-2-kinase by protein kinase C and comparison of the fructose-2,6-bisphosphatase activity of the two enzymes, 10.1042/bj2400057
  33. Sutherland C, Leighton I A, Cohen P, Inactivation of glycogen synthase kinase-3βby phosphorylation: new kinase connections in insulin and growth-factor signalling, 10.1042/bj2960015
  34. Depre, J. Biol. Chem., 268, 13274 (1993)
  35. Flotow, J. Biol. Chem., 267, 3074 (1992)
  36. Alessi Dario R., Barry Caudwell F., Andjelkovic Mirjana, Hemmings Brian A., Cohen Philip, Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase-1 and p70 S6 kinase, 10.1016/s0014-5793(96)01370-1
  37. Lefebvre Véronique, Méchin Marie-Claire, Louckx Marc P., Rider Mark H., Hue Louis, Signaling Pathway Involved in the Activation of Heart 6-Phosphofructo-2-kinase by Insulin, 10.1074/jbc.271.37.22289
  38. Saltiel, Am. J. Physiol., 270, E375 (1996)
  39. LAVOINNE Alain, ERIKSON Eleanor, MALLER James L., PRICE Daniel J., AVRUCH Joseph, COHEN Philip, Purification and characterisation of the insulin-stimulated protein kinase from rabbit skeletal muscle; close similarity to S6 kinase II, 10.1111/j.1432-1033.1991.tb16176.x
  40. Chung Jongkyeong, Grammar Timothy C., Lemon Katherine P., Kazlauskas Andrius, Blenis John, PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase, 10.1038/370071a0
  41. Burgering Boudewijn M. Th., Coffer Paul J., Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction, 10.1038/376599a0
Bibliographic reference Deprez, J ; Vertommen, Didier ; Alessi, Dario R. ; Hue, Louis ; Rider, Mark H.. Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. In: Journal of Biological Chemistry, Vol. 272, no. 28, p. 17269-17275 (1997)
Permanent URL http://hdl.handle.net/2078.1/22004