Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M209153200 on January 1, 2003

J. Biol. Chem., Vol. 278, Issue 10, 8199-8211, March 7, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/10/8199    most recent
M209153200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Greene, M. W.
Right arrow Articles by Roth, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Greene, M. W.
Right arrow Articles by Roth, R. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Modulation of Insulin-stimulated Degradation of Human Insulin Receptor Substrate-1 by Serine 312 Phosphorylation*

Michael W. GreeneDagger , Hiroshi SakaueDagger , Lihong WangDagger , Dario R. Alessi§, and Richard A. RothDagger

From the Dagger  Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305 and the § Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, Department of Biochemistry, Wellcome Trust Building, MSI/WTB Complex, University of Dundee, Dundee DD1 5EH , Scotland, United Kingdom

Ser/Thr phosphorylation of insulin receptor substrate-1 (IRS-1) is a negative regulator of insulin signaling. One potential mechanism for this is that Ser/Thr phosphorylation decreases the ability of IRS-1 to be tyrosine-phosphorylated by the insulin receptor. An additional mechanism for modulating insulin signaling is via the down-regulation of IRS-1 protein levels. Insulin-induced degradation of IRS-1 has been well documented, both in cells as well as in patients with diabetes. Ser/Thr phosphorylation of IRS-1 correlates with IRS-1 degradation, yet the details of how this occurs are still unknown. In the present study we have examined the potential role of different signaling cascades in the insulin-induced degradation of IRS-1. First, we found that inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin block the degradation. Second, knockout cells lacking one of the key effectors of this cascade, the phosphoinositide-dependent kinase-1, were found to be deficient in the insulin-stimulated degradation of IRS-1. Conversely, overexpression of this enzyme potentiated insulin-stimulated IRS-1 degradation. Third, concurrent with the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin also blocked the insulin-stimulated increase in Ser312 phosphorylation. Most important, an IRS-1 mutant in which Ser312 was changed to alanine was found to be resistant to insulin-stimulated IRS-1 degradation. Finally, an inhibitor of c-Jun N-terminal kinase, SP600125, at 10 µM did not block IRS-1 degradation and IRS-1 Ser312 phosphorylation yet completely blocked insulin-stimulated c-Jun phosphorylation. Further, insulin-stimulated c-Jun phosphorylation was not blocked by inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin, indicating that c-Jun N-terminal kinase is unlikely to be the kinase phosphorylating IRS-1 Ser312 in response to insulin. In summary, our results indicate that the insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the Ser312 phosphorylation of IRS-1.

* This work was supported in part by National Institutes of Health Grant DK34976 (to R. A. R.) and an American Diabetes Association mentor-based postdoctoral fellowship (to H. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Molecular Pharmacology, Stanford University School of Medicine, Rm. 3145B, CCSR, 269 Campus Dr., Stanford, CA 94305-5174. Tel.: 650-723-5933; Fax: 650-723-2253; E-mail: rroth@stanford.edu.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
S. Boura-Halfon and Y. Zick
Phosphorylation of IRS proteins, insulin action, and insulin resistance
Am J Physiol Endocrinol Metab, April 1, 2009; 296(4): E581 - E591.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Zhang, Z. Gao, J. Yin, M. J. Quon, and J. Ye
S6K Directly Phosphorylates IRS-1 on Ser-270 to Promote Insulin Resistance in Response to TNF-{alpha} Signaling through IKK2
J. Biol. Chem., December 19, 2008; 283(51): 35375 - 35382.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. Weigert, M. Kron, H. Kalbacher, A. K. Pohl, H. Runge, H.-U. Haring, E. Schleicher, and R. Lehmann
Interplay and Effects of Temporal Changes in the Phosphorylation State of Serine-302, -307, and -318 of Insulin Receptor Substrate-1 on Insulin Action in Skeletal Muscle Cells
Mol. Endocrinol., December 1, 2008; 22(12): 2729 - 2740.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
N. Kumashiro, Y. Tamura, T. Uchida, T. Ogihara, Y. Fujitani, T. Hirose, H. Mochizuki, R. Kawamori, and H. Watada
Impact of Oxidative Stress and Peroxisome Proliferator-Activated Receptor {gamma} Coactivator-1{alpha} in Hepatic Insulin Resistance
Diabetes, August 1, 2008; 57(8): 2083 - 2091.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. S. Waraich, C. Weigert, H. Kalbacher, A. M. Hennige, S. Z. Lutz, H.-U. Haring, E. D. Schleicher, W. Voelter, and R. Lehmann
Phosphorylation of Ser357 of Rat Insulin Receptor Substrate-1 Mediates Adverse Effects of Protein Kinase C-{delta} on Insulin Action in Skeletal Muscle Cells
J. Biol. Chem., April 25, 2008; 283(17): 11226 - 11233.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Luo, P. Langlais, Z. Yi, N. Lefort, E. A. De Filippis, H. Hwang, C. Y. Christ-Roberts, and L. J. Mandarino
Phosphorylation of Human Insulin Receptor Substrate-1 at Serine 629 Plays a Positive Role in Insulin Signaling
Endocrinology, October 1, 2007; 148(10): 4895 - 4905.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Giraud, M. Haas, E. P. Feener, K. D. Copps, X. Dong, S. L. Dunn, and M. F. White
Phosphorylation of Irs1 at SER-522 Inhibits Insulin Signaling
Mol. Endocrinol., September 1, 2007; 21(9): 2294 - 2302.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
P. Newsholme, E. P. Haber, S. M. Hirabara, E. L. O. Rebelato, J. Procopio, D. Morgan, H. C. Oliveira-Emilio, A. R. Carpinelli, and R. Curi
Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity
J. Physiol., August 15, 2007; 583(1): 9 - 24.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Z. Yi, P. Langlais, E. A. De Filippis, M. Luo, C. R. Flynn, S. Schroeder, S. T. Weintraub, R. Mapes, and L. J. Mandarino
Global Assessment of Regulation of Phosphorylation of Insulin Receptor Substrate-1 by Insulin In Vivo in Human Muscle
Diabetes, June 1, 2007; 56(6): 1508 - 1516.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H.-Y. Liu, Q. F. Collins, Y. Xiong, F. Moukdar, E. G. Lupo Jr., Z. Liu, and W. Cao
Prolonged Treatment of Primary Hepatocytes with Oleate Induces Insulin Resistance through p38 Mitogen-activated Protein Kinase
J. Biol. Chem., May 11, 2007; 282(19): 14205 - 14212.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
M. P Corcoran, S. Lamon-Fava, and R. A Fielding
Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise
Am. J. Clinical Nutrition, March 1, 2007; 85(3): 662 - 677.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
P. K. Mehta and K. K. Griendling
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system
Am J Physiol Cell Physiol, January 1, 2007; 292(1): C82 - C97.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
E. R. Ropelle, J. R. Pauli, P. O. Prada, C. T. de Souza, P. K. Picardi, M. C. Faria, D. E. Cintra, M. F. d. A. Fernandes, M. B. Flores, L. A. Velloso, et al.
Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation
J. Physiol., December 15, 2006; 577(3): 997 - 1007.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. M. Hennige, N. Stefan, K. Kapp, R. Lehmann, C. Weigert, A. Beck, K. Moeschel, J. Mushack, E. Schleicher, and H.-U. Haring
Leptin down-regulates insulin action through phosphorylation of serine-318 in insulin receptor substrate 1
FASEB J, June 1, 2006; 20(8): 1206 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. Corbould, H. Zhao, S. Mirzoeva, F. Aird, and A. Dunaif
Enhanced Mitogenic Signaling in Skeletal Muscle of Women With Polycystic Ovary Syndrome
Diabetes, March 1, 2006; 55(3): 751 - 759.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Scioscia, K. Gumaa, S. Kunjara, M. A. Paine, L. E. Selvaggi, C. H. Rodeck, and T. W. Rademacher
Insulin Resistance in Human Preeclamptic Placenta Is Mediated by Serine Phosphorylation of Insulin Receptor Substrate-1 and -2
J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 709 - 717.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. Kim, C. M. van Golen, and E. L. Feldman
Insulin-Like Growth Factor I Induces Preferential Degradation of Insulin Receptor Substrate-2 through the Phosphatidylinositol 3-Kinase Pathway in Human Neuroblastoma Cells
Endocrinology, December 1, 2005; 146(12): 5350 - 5357.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Danielsson, A. Ost, F. H. Nystrom, and P. Stralfors
Attenuation of Insulin-stimulated Insulin Receptor Substrate-1 Serine 307 Phosphorylation in Insulin Resistance of Type 2 Diabetes
J. Biol. Chem., October 14, 2005; 280(41): 34389 - 34392.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
Y. Shi, H. Yan, P. Frost, J. Gera, and A. Lichtenstein
Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade
Mol. Cancer Ther., October 1, 2005; 4(10): 1533 - 1540.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
F. Tremblay, M. Krebs, L. Dombrowski, A. Brehm, E. Bernroider, E. Roth, P. Nowotny, W. Waldhausl, A. Marette, and M. Roden
Overactivation of S6 Kinase 1 as a Cause of Human Insulin Resistance During Increased Amino Acid Availability
Diabetes, September 1, 2005; 54(9): 2674 - 2684.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
F. S. L. Thong, C. B. Dugani, and A. Klip
Turning Signals On and Off: GLUT4 Traffic in the Insulin-Signaling Highway
Physiology, August 1, 2005; 20(4): 271 - 284.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Y. Jiang, Q. L. Zhou, J. Holik, S. Patel, J. Leszyk, K. Coleman, M. Chouinard, and M. P. Czech
Identification of WNK1 as a Substrate of Akt/Protein Kinase B and a Negative Regulator of Insulin-stimulated Mitogenesis in 3T3-L1 Cells
J. Biol. Chem., June 3, 2005; 280(22): 21622 - 21628.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
Y. Taniyama, H. Hitomi, A. Shah, R. W. Alexander, and K. K. Griendling
Mechanisms of Reactive Oxygen Species-Dependent Downregulation of Insulin Receptor Substrate-1 by Angiotensin II
Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1142 - 1147.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. Corbould, Y.-B. Kim, J. F. Youngren, C. Pender, B. B. Kahn, A. Lee, and A. Dunaif
Insulin resistance in the skeletal muscle of women with PCOS involves intrinsic and acquired defects in insulin signaling
Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E1047 - E1054.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Sugita, M. Fujimoto, T. Yasukawa, N. Shimizu, M. Sugita, S. Yasuhara, J. A. J. Martyn, and M. Kaneki
Inducible Nitric-oxide Synthase and NO Donor Induce Insulin Receptor Substrate-1 Degradation in Skeletal Muscle Cells
J. Biol. Chem., April 8, 2005; 280(14): 14203 - 14211.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. M. Brachmann, K. Ueki, J. A. Engelman, R. C. Kahn, and L. C. Cantley
Phosphoinositide 3-Kinase Catalytic Subunit Deletion and Regulatory Subunit Deletion Have Opposite Effects on Insulin Sensitivity in Mice
Mol. Cell. Biol., March 1, 2005; 25(5): 1596 - 1607.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. Döhr, A. Klingenhoff, H. Maier, M. H. de Angelis, T. Werner, and R. Schneider
Linking disease-associated genes to regulatory networks via promoter organization
Nucleic Acids Res., February 8, 2005; 33(3): 864 - 872.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
B. D. Manning
Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis
J. Cell Biol., November 8, 2004; 167(3): 399 - 403.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. D. Werner, J. Lee, L. Hansen, M. Yuan, and S. E. Shoelson
Insulin Resistance Due to Phosphorylation of Insulin Receptor Substrate-1 at Serine 302
J. Biol. Chem., August 20, 2004; 279(34): 35298 - 35305.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
Z. Gao, X. Zhang, A. Zuberi, D. Hwang, M. J. Quon, M. Lefevre, and J. Ye
Inhibition of Insulin Sensitivity by Free Fatty Acids Requires Activation of Multiple Serine Kinases in 3T3-L1 Adipocytes
Mol. Endocrinol., August 1, 2004; 18(8): 2024 - 2034.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
W. H. Shen, Y. Yin, S. R. Broussard, R. H. McCusker, G. G. Freund, R. Dantzer, and K. W. Kelley
Tumor Necrosis Factor {alpha} Inhibits Cyclin A Expression and Retinoblastoma Hyperphosphorylation Triggered by Insulin-like Growth Factor-I Induction of New E2F-1 Synthesis
J. Biol. Chem., February 27, 2004; 279(9): 7438 - 7446.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
T. E. Harris and J. C. Lawrence Jr.
TOR Signaling
Sci. Signal., December 9, 2003; 2003(212): re15 - re15.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Gual, T. Gonzalez, T. Gremeaux, R. Barres, Y. Le Marchand-Brustel, and J.-F. Tanti
Hyperosmotic Stress Inhibits Insulin Receptor Substrate-1 Function by Distinct Mechanisms in 3T3-L1 Adipocytes
J. Biol. Chem., July 11, 2003; 278(29): 26550 - 26557.
[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 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement