| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 6, 3198-3204, February 6, 1998
,, and
From the Department of Molecular Physiology and Biophysics,
Vanderbilt University, Nashville, Tennessee 37232-0615 and the
Phosphoenolpyruvate carboxykinase (PEPCK)
catalyzes the first committed step in hepatic gluconeogenesis. Glucagon
and glucocorticoids stimulate PEPCK gene transcription, whereas insulin
has a dominant inhibitory effect. We have shown that inhibitors of
1-phosphatidylinositol 3-kinase (PI 3-kinase) block this action of
insulin. In contrast, three distinct agents, all of which prevent
activation of p42/p44 mitogen-activated protein (MAP) kinase, have no
effect on the regulation of PEPCK transcription by insulin. However, a
subsequent report has suggested that this pathway is involved in the
inhibition of cAMP-induced PEPCK gene transcription by insulin. To
address these conflicting data, we re-examined the Ras MAP kinase
pathway, not only with respect to regulation of PEPCK gene
transcription, but also for regulation of PI 3-kinase and p42/p44 MAP
kinase. Overexpression of constitutively active Ras (V61) (or Raf-1
(RafCAAX)) partially represses PEPCK transcription in
hepatoma cells. However, an inhibitor of MAP kinase kinase blocks this
action of RafCAAX but has no effect on regulation of PEPCK
gene transcription by insulin. Second, the action of a dominant
negative Ras (N17Ras) on PEPCK gene transcription correlates more
closely with the inhibition of PI 3-kinase than with the inhibition of
p42/p44 MAP kinase. Third, insulin cannot activate p42/p44 MAP kinase
in the presence of cAMP even though cAMP-induced PEPCK gene
transcription is inhibited by insulin. This data confirms that the Ras
MAP kinase pathway is not required for the regulation of PEPCK gene
transcription by insulin and demonstrates the importance of employing
multiple techniques when investigating the function of signaling
pathways.
Diabetes Unit, Division of Endocrinology and Metabolism,
Department of Medicine, Beth Israel Deaconess Medical Center and
Harvard Medical School, Boston, Massachusetts 02215
This article has been cited by other articles:
|
|
 |
|
  B. Draznin Molecular Mechanisms of Insulin Resistance: Serine Phosphorylation of Insulin Receptor Substrate-1 and Increased Expression of p85{alpha}: The Two Sides of a Coin. Diabetes, August 1, 2006; 55(8): 2392 - 2397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xu, Q. Yang, M. Shen, X. Huang, M. Dembski, R. Gimeno, L. A. Tartaglia, R. Kapeller, and Z. Wu Dual Specificity MAPK Phosphatase 3 Activates PEPCK Gene Transcription and Increases Gluconeogenesis in Rat Hepatoma Cells J. Biol. Chem., October 28, 2005; 280(43): 36013 - 36018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nowak, A. Helleboid-Chapman, H. Jakel, G. Martin, D. Duran-Sandoval, B. Staels, E. M. Rubin, L. A. Pennacchio, M.-R. Taskinen, J. Fruchart-Najib, et al. Insulin-Mediated Down-Regulation of Apolipoprotein A5 Gene Expression through the Phosphatidylinositol 3-Kinase Pathway: Role of Upstream Stimulatory Factor Mol. Cell. Biol., February 15, 2005; 25(4): 1537 - 1548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ueki, D. A. Fruman, C. M. Yballe, M. Fasshauer, J. Klein, T. Asano, L. C. Cantley, and C. R. Kahn Positive and Negative Roles of p85{alpha} and p85{beta} Regulatory Subunits of Phosphoinositide 3-Kinase in Insulin Signaling J. Biol. Chem., November 28, 2003; 278(48): 48453 - 48466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Barthel and D. Schmoll Novel concepts in insulin regulation of hepatic gluconeogenesis Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E685 - E692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, M. Dembski, Q. Yang, D. Yang, A. Moriarty, O. Tayber, H. Chen, R. Kapeller, and L. A. Tartaglia Dual Specificity Mitogen-activated Protein (MAP) Kinase Phosphatase-4 Plays a Potential Role in Insulin Resistance J. Biol. Chem., August 8, 2003; 278(32): 30187 - 30192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Young Lee, C.-H. Jung, K. Lee, Y. Hyun Choi, S. Hong, and J. Cheong Activating Transcription Factor-2 Mediates Transcriptional Regulation of Gluconeogenic Gene PEPCK by Retinoic Acid Diabetes, December 1, 2002; 51(12): 3400 - 3407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Patel, P. A. Lochhead, G. Rena, S. Fumagalli, M. Pende, S. C. Kozma, G. Thomas, and C. Sutherland Insulin Regulation of Insulin-like Growth Factor-binding Protein-1 Gene Expression Is Dependent on the Mammalian Target of Rapamycin, but Independent of Ribosomal S6 Kinase Activity J. Biol. Chem., March 15, 2002; 277(12): 9889 - 9895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Murata, Y. Okimura, K. Iida, M. Matsumoto, H. Sowa, H. Kaji, M. Kojima, K. Kangawa, and K. Chihara Ghrelin Modulates the Downstream Molecules of Insulin Signaling in Hepatoma Cells J. Biol. Chem., February 8, 2002; 277(7): 5667 - 5674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Lochhead, M. Coghlan, S. Q.J. Rice, and C. Sutherland Inhibition of GSK-3 Selectively Reduces Glucose-6-Phosphatase and Phosphoenolpyruvate Carboxykinase Gene Expression Diabetes, May 1, 2001; 50(5): 937 - 946. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. N. Kaytor, J. L. Zhu, C.-I Pao, and L. S. Phillips Physiological Concentrations of Insulin Promote Binding of Nuclear Proteins to the Insulin-Like Growth Factor I Gene Endocrinology, March 1, 2001; 142(3): 1041 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Carrillo, B. Ibares, A. Esteban-Gamboa, and J. E. Feliu Involvement of Both Phosphatidylinositol 3-Kinase and p44/p42 Mitogen-Activated Protein Kinase Pathways in the Short-Term Regulation of Pyruvate Kinase L by Insulin Endocrinology, March 1, 2001; 142(3): 1057 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Cefalu Insulin Resistance: Cellular and Clinical Concepts Experimental Biology and Medicine, January 1, 2001; 226(1): 13 - 26. [Abstract] [Full Text]
|
|
|
|
|
|
H. Iwasaki, S. Eguchi, H. Ueno, F. Marumo, and Y. Hirata Endothelin-Mediated Vascular Growth Requires p42/p44 Mitogen-Activated Protein Kinase and p70 S6 Kinase Cascades via Transactivation of Epidermal Growth Factor Receptor Endocrinology, October 1, 1999; 140(10): 4659 - 4668. [Abstract] [Full Text]
|
|
|
|
|
|
K. Kotani, W. Ogawa, Y. Hino, T. Kitamura, H. Ueno, W. Sano, C. Sutherland, D. K. Granner, and M. Kasuga Dominant Negative Forms of Akt (Protein Kinase B) and Atypical Protein Kinase Clambda Do Not Prevent Insulin Inhibition of Phosphoenolpyruvate Carboxykinase Gene Transcription J. Biol. Chem., July 23, 1999; 274(30): 21305 - 21312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Rena, S. Guo, S. C. Cichy, T. G. Unterman, and P. Cohen Phosphorylation of the Transcription Factor Forkhead Family Member FKHR by Protein Kinase B J. Biol. Chem., June 11, 1999; 274(24): 17179 - 17183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liao, A. Barthel, K. Nakatani, and R. A. Roth Activation of Protein Kinase B/Akt Is Sufficient to Repress the Glucocorticoid and cAMP Induction of Phosphoenolpyruvate Carboxykinase Gene J. Biol. Chem., October 16, 1998; 273(42): 27320 - 27324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang and H. S. Sul Insulin Stimulation of the Fatty Acid Synthase Promoter Is Mediated by the Phosphatidylinositol 3-Kinase Pathway. INVOLVEMENT OF PROTEIN KINASE B/Akt J. Biol. Chem., September 25, 1998; 273(39): 25420 - 25426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Agati, D. Yeagley, and P. G. Quinn Assessment of the Roles of Mitogen-activated Protein Kinase, Phosphatidylinositol 3-Kinase, Protein Kinase B, and Protein Kinase C in Insulin Inhibition of cAMP-induced Phosphoenolpyruvate Carboxykinase Gene Transcription J. Biol. Chem., July 24, 1998; 273(30): 18751 - 18759. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
