| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574; 2 Third Department of Internal Medicine, Yamaguchi University School of Medicine, Yamaguchi 755-8505; 3 Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8566; 4 Fourth Department of Medicine, Saitama Medical School, Saitama 350-0495; 5 Institute for Adult Disease, Asahi Life Foundation, Tokyo 160; 6 Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan
To investigate the role of
3-phosphoinositide-dependent protein kinase 1 (PDK1) in the
insulin-signaling pathway for glucose metabolism, wild-type (wt), the
kinase-dead (kd), or the plecstrin homology (PH) domain deletion
(
PH) mutant of PDK1 was expressed using an adenovirus gene
transduction system in 3T3-L1 adipocytes. wt-PDK1 and kd-PDK1 were
found in both membrane and cytosol fractions, whereas PH-PDK1, which
exhibited PDK1 activity similar to that of wt-PDK1, was detected
exclusively in the cytosol fraction. Insulin dose dependently activated
protein kinase B (PKB) but did not change atypical protein kinase C
(aPKC) activity in control cells. aPKC activity was not affected by
expression of wt-, kd-, or PH-PDK1 in either the presence or the
absence of insulin. Overexpression of wt-PDK1 enhanced insulin-induced
activation of PKB as well as insulin-induced phosphorylation of
glycogen synthase kinase (GSK)3
/
, a direct downstream target of
PKB, although insulin-induced glycogen synthesis was not significantly enhanced by wt-PDK1 expression. Neither PH-PDK1 nor kd-PDK1
expression affected PKB activity, GSK3 phosphorylation, or glycogen
synthesis. Thus membrane localization of PDK1 via its PH domain is
essential for insulin signaling through the PDK1-PKB-GSK3/
pathway. Glucose transport activity was unaffected by expression of
wt-PDK1, kd-PDK1, or PH-PDK1 in either the presence or the absence
of insulin. These findings suggest the presence of a signaling pathway
for insulin-stimulated glucose transport in which PDK1 to PKB or aPKC is not involved.
glycogen synthesis; glucose transport; GLUT4; protein kinase B; protein kinase C
This article has been cited by other articles:
|
|
 |
|
  J. Chunqiu Hou and J. E. Pessin Lipid Raft Targeting of the TC10 Amino Terminal Domain Is Responsible for Disruption of Adipocyte Cortical Actin Mol. Biol. Cell, September 1, 2003; 14(9): 3578 - 3591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-B. Kim, K. Kotani, T. P. Ciaraldi, R. R. Henry, and B. B. Kahn Insulin-Stimulated Protein Kinase C {lambda}/{zeta} Activity Is Reduced in Skeletal Muscle of Humans With Obesity and Type 2 Diabetes: Reversal With Weight Reduction Diabetes, August 1, 2003; 52(8): 1935 - 1942. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
