MAINTENANCE EN COURS / SITE UNDER MAINTENANCE

Une opération de maintenance est en cours: les résultats de recherches et les exportations peuvent être incohérent.
Site under maintenance: search & exportation results could be inconsistent.
 

Heart 6-phosphofructo-2-kinase activation by insulin results from Ser-466 and Ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase B.

Bertrand, Luc;Alessi, Dario R.;Deprez, Johan;Deak, Maria;Hue, Louis;et.al.
(1999) Journal of Biological Chemistry — Vol. 274, n° 43, p. 30927-30933 (1999)

Files

BERTRAND_JBC1999.pdf
  • Restricted Access
  • Adobe PDF
  • 294.27 KB
Request a copy

Details

Authors
  • Bertrand, LucUCLouvain
    Author
  • Alessi, Dario R.
    Author
  • Deprez, JohanUCLouvain
    Author
  • Deak, Maria
    Author
  • Viaene, EricUCLouvain
    Author
  • Rider, Mark H.UCLouvain
    Author
  • Hue, LouisUCLouvain
    Author
Show more
Abstract
Previous studies have shown that (i) the insulin-induced activation of heart 6-phosphofructo-2-kinase (PFK-2) is wortmannin-sensitive, but is insensitive to rapamycin, suggesting the involvement of phosphatidylinositol 3-kinase; and (ii) protein kinase B (PKB) activates PFK-2 in vitro by phosphorylating Ser-466 and Ser-483. In this work, we have studied the effects of phosphorylation of these residues on PFK-2 activity by replacing each or both residues with glutamate. Mutation of Ser-466 increased the V(max) of PFK-2, whereas mutation of Ser-483 decreased citrate inhibition. Mutation of both residues was required to decrease the K(m) for fructose 6-phosphate. We also studied the insulin-induced activation of heart PFK-2 in transfection experiments performed in human embryonic kidney 293 cells. Insulin activated transfected PFK-2 by phosphorylating Ser-466 and Ser-483. Kinase-dead (KD) PKB and KD 3-phosphoinositide-dependent kinase-1 (PDK-1) cotransfectants acted as dominant negatives because both prevented the insulin-induced activation of PKB as well as the inactivation of glycogen-synthase kinase-3, an established substrate of PKB. However, the insulin-induced activation of PFK-2 was prevented only by KD PDK-1, but not by KD PKB. These results indicate that the insulin-induced activation of heart PFK-2 is mediated by a PDK-1-activated protein kinase other than PKB.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Bertrand, L., Alessi, D. R., Deprez, J., Deak, M., Viaene, E., Rider, M. H., & Hue, L. (1999). Heart 6-phosphofructo-2-kinase activation by insulin results from Ser-466 and Ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase B. Journal of Biological Chemistry, 274(43), 30927-30933. https://hdl.handle.net/2078.5/212068 (Original work published 1999)