Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action

Eldar-Finkelman, Hagit; Krebs, Edwin G.

doi:10.1073/pnas.94.18.9660

Cited by 319Metabolism, Diabetes, and CancerProtein Kinase Regulation and GTPase SignalingWnt/β-catenin signaling in development and cancer

Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action

Open access

Eldar-Finkelman, Hagit, Krebs, Edwin G.·1997·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.94.18.9660PMC PMC23245

Open this paper in CoChat — free account Open PDF

Abstract

The phosphorylation of insulin receptor substrate 1 (IRS-1) on tyrosine residues by the insulin receptor (IR) tyrosine kinase is involved in most of the biological responses of insulin. IRS-1 mediates insulin signaling by recruiting SH2 proteins through its multiple tyrosine phosphorylation sites. The phosphorylation of IRS-1 on serine/threonine residues also occurs in cells; however, the particular protein kinase(s) promoting this type of phosphorylation are unknown. Here we report that glycogen synthase kinase 3 (GSK-3) is capable of phosphorylating IRS-1 and that this modification converts IRS-1 into an inhibitor of IR tyrosine kinase activity in vitro . Expression of wild-type GSK-3 or an “unregulated” mutant of the kinase (S9A) in CHO cells overexpressing IRS-1 and IR, resulted in increased serine phosphorylation levels of IRS-1, suggesting that IRS-1 is a cellular target of GSK-3. Furthermore, insulin-induced tyrosine phosphorylation of IRS-1 and IR was markedly suppressed in cells expressing wild-type or the S9A mutant, indicating that expression of GSK-3 impairs IR tyrosine kinase activity. Taken together, our studies suggest a new role for GSK-3 in attenuating insulin signaling via its phosphorylation of IRS-1 and may provide new insight into mechanisms important in insulin resistance.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1073/pnas.94.18.9660

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

GSK-3 phosphorylates IRS-1, which reduces activation of PI 3-kinase and PKB.
“GSK-3 has been reported to phosphorylate IRS-1, which reduces activation of PI 3-kinase and PKB [49].”
From Glucocorticoid-induced insulin resistance in skeletal muscles: defects in insulin signalling and the effects of a selective glycogen synthase kinase-3 inhibitor (2005) · cites this paper as [49]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

IRS-1-Mediated Inhibition of Insulin Receptor Tyrosine Kinase Activity in TNF-α- and Obesity-Induced Insulin Resistance
Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.271.5249.665 · Cited by 2,630 · see citing works
Elective induction versus spontaneous labor after sonographic diagnosis of fetal macrosomia.
Combs, C. A., Singh, N. B., & Khoury, J. C. (1993) · PubMed · Cited by 2,462 · see citing works
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
Sun, X. J., Rothenberg, P., Kahn, C. R., Backer, J. M., Araki, E., Wilden, P. A., Cahill, D. A., Goldstein, B. J., & White, M. F. (1991) · Nature · doi:10.1038/352073a0 · Cited by 1,574 · see citing works
Tumor necrosis factor alpha inhibits signaling from the insulin receptor.
Hotamışlıgil, G. S., Murray, D. L., Choy, L., & Spiegelman, B. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.11.4854 · Cited by 1,206 · see citing works
Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity
Boyle, W. J., Smeal, T., Defize, L. H. K., Angel, P. E., Woodgett, J. R., Karin, M., & Hunter, T. R. (1991) · Cell · doi:10.1016/0092-8674(91)90241-p · Cited by 1,036 · see citing works
Inactivation of glycogen synthase kinase-3 <i>β</i> by phosphorylation: new kinase connections in insulin and growth-factor signalling
Sutherland, C., Leighton, I. A., & Cohen, P. (1993) · Biochemical Journal · doi:10.1042/bj2960015 · Cited by 903 · see citing works
The Function of GRB2 in Linking the Insulin Receptor to Ras Signaling Pathways
Skolnik, E. Y., Batzer, A., Li, N., Lee, C., Lowenstein, E. J., Mohammadi, M., Margolis, B. L., & Schlessinger, J. (1993) · Science · doi:10.1126/science.8316835 · Cited by 632 · see citing works
Mitogen inactivation of glycogen synthase kinase-3β in intact cells via serine 9 phosphorylation
Stambolic, V., & Woodgett, J. R. (1994) · Biochemical Journal · doi:10.1042/bj3030701 · Cited by 581 · see citing works
Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos
He, X., Saint‐Jeannet, J., Woodgett, J. R., VARMUS, H. E., & Dawid, I. B. (1995) · Nature · doi:10.1038/374617a0 · Cited by 490 · see citing works
Overproduction of protein kinase C causesdisordered growth control in rat fibroblasts
Housey, G. M., Johnson, M. D., Hsiao, W. L. W., O’Brian, C. A., Murphy, J. P., Kirschmeier, P. T., & Weinstein, I. B. (1988) · Cell · doi:10.1016/s0092-8674(88)80027-8 · Cited by 478 · see citing works
IRS-1 activates phosphatidylinositol 3'-kinase by associating with src homology 2 domains of p85.
Myers, M. G., Backer, J., Sun, X., Shoelson, S. E., Hu, P. J., Schlessinger, J., Yoakim, M., Schaffhausen, B. S., & White, M. F. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10350 · Cited by 478 · see citing works
The inhibition of glycogen synthase kinase-3 by insulin or insulin-like growth factor 1 in the rat skeletal muscle cell line L6 is blocked by wortmannin, but not by rapamycin: evidence that wortmannin blocks activation of the mitogen-activated protein kinase pathway in L6 cells between Ras and Raf
Cross, D. A. E., Alessi, D. R., Vandenheede, J. R., McDowell, H. E., Hundal, H. S., & Cohen, P. (1994) · Biochemical Journal · doi:10.1042/bj3030021 · Cited by 474 · see citing works
Acid and base hydrolysis of phosphoproteins bound to Immobilon facilitates analysis of phosphoamino acids in gel-fractionated proteins
Kamps, M. P., & Sefton, B. M. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90266-2 · Cited by 459 · see citing works
Tumor Necrosis Factor α-induced Phosphorylation of Insulin Receptor Substrate-1 (IRS-1)
Kanety, H., Feinstein, R., Papa, M. Z., Hemi, R., & Karasik, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.40.23780 · Cited by 435 · see citing works
wingless signaling acts through zeste-white 3, the drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fate
Siegfried, E., Chou, T.-B., & Perrimon, N. (1992) · Cell · doi:10.1016/s0092-8674(05)80065-0 · Cited by 423 · see citing works
Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B
Welsh, G. I., & Proud, C. G. (1993) · Biochemical Journal · doi:10.1042/bj2940625 · Cited by 397 · see citing works
The role of protein phosphorylation in the hormonal control of enzyme activity
Cohen, P. (1985) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1985.tb09121.x · Cited by 379 · see citing works
Glycogen synthase kinase-3: functions in oncogenesis and development
Plyte, S. E. (1992) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(92)90012-n · Cited by 377 · see citing works
Insulin Signal Transduction and the IRS Proteins
Myers, M. G., & White, M. F. (1996) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.36.040196.003151 · Cited by 333 · see citing works
Expression and function of IRS-1 in insulin signal transmission.
Sun, X. J., Miralpeix, M., Myers, M. G., Glasheen, E. M., Backer, J. M., Kahn, C. R., & White, M. F. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41723-1 · Cited by 326 · see citing works
Serine/threonine phosphorylation of insulin receptor substrate 1 modulates insulin receptor signaling.
Tanti, J., Grémeaux, T., OBBERGHEN, E. V., & MARCHAND‐BRUSTEL, Y. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37568-3 · Cited by 309 · see citing works
Glycogen synthase kinase-3 beta is a dual specificity kinase differentially regulated by tyrosine and serine/threonine phosphorylation.
Wang, Q. M., Fiol, C. J., DePaoli-Roach, A. A., & Roach, P. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36661-9 · Cited by 289 · see citing works
A secondary phosphorylation of CREB341 at Ser129 is required for the cAMP-mediated control of gene expression. A role for glycogen synthase kinase-3 in the control of gene expression.
Fiol, C. J., Williams, J. S., Chou, C. H., Wang, Q. M., Roach, P. J., & ANDRISANI, O. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31619-3 · Cited by 278 · see citing works
Regulation of Spemann organizer formation by the intracellular kinase Xgsk-3
Pierce, S. B., & Kimelman, D. (1995) · Development · doi:10.1242/dev.121.3.755 · Cited by 230 · see citing works
Inactivation of Glycogen Synthase Kinase-3 by Epidermal Growth Factor Is Mediated by Mitogen-activated Protein Kinase/p90 Ribosomal Protein S6 Kinase Signaling Pathway in NIH/3T3 Cells
Eldar-Finkelman, H., Seger, R., Vandenheede, J. R., & Krebs, E. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.987 · Cited by 214 · see citing works
Self-citation
Nck associates with the SH2 domain-docking protein IRS-1 in insulin-stimulated cells.
Lee, C., Li, W., Nishimura, R., Zhou, M., Batzer, A., Myers, M. G., White, M. F., Schlessinger, J., & Skolnik, E. Y. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.24.11713 · Cited by 211 · see citing works
Tyrosyl phosphorylation and growth factor receptor association of the human corkscrew homologue, SH-PTP2
Lechleider, R. J., Freeman, R. M., & Neel, B. G. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38668-5 · Cited by 191 · see citing works
GSK3: a SHAGGY frog story
Welsh, G. I., WILSON, C. G., & Proud, C. G. (1996) · Trends in Cell Biology · doi:10.1016/0962-8924(96)10023-4 · Cited by 149 · see citing works
Expression and characterization of glycogen synthase kinase-3 mutants and their effect on glycogen synthase activity in intact cells.
Eldar-Finkelman, H., Argast, G. M., Foord, O., Fischer, E. H., & Krebs, E. G. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.19.10228 · Cited by 143 · see citing works
Self-citation
Diverse signaling pathways in the cellular actions of insulin
Saltiel, A. R. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.3.e375 · Cited by 142 · see citing works
Insulin receptor substrate-1 (IRS1) and Shc compete for a limited pool of Grb2 in mediating insulin downstream signaling.
Yamauchi, K., & Pessin, J. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47396-6 · Cited by 112 · see citing works
Molecular Actions of Insulin on Glucose Transport
Czech, M. (1995) · Annual Review of Nutrition · doi:10.1146/annurev.nu.15.070195.002301 · Cited by 95 · see citing works
Phosphorylation of the insulin receptor substrate IRS-1 by casein kinase II.
Tanasijevic, M. J., Myers, M. G., Thoma, R. S., Crimmins, D. L., White, M. F., & Sacks, D. B. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)46824-4 · Cited by 83 · see citing works
Characterization of affinity-purified insulin receptor/kinase. Effects of dithiothreitol on receptor/kinase function.
PIKE, L. J., Eakes, A. T., & Krebs, E. G. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)35716-2 · Cited by 76 · see citing works
Self-citation
Overexpression of protein kinase C alpha-subtype in Swiss/3T3 fibroblasts causes loss of both high and low affinity receptor numbers for epidermal growth factor.
Eldar-Finkelman, H., Zisman, Y., Ullrich, A., et al. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38297-3 · Cited by 74 · see citing works
Self-citation
Regulation of casein kinase II by growth factors: a reevaluation.
Litchfield, D. W., Dobrowolska, G., & Krebs, E. G. (1994) · PubMed · Cited by 70 · see citing works
Self-citation
Differential regulation of S6 phosphorylation by insulin and epidermal growth factor in Swiss mouse 3T3 cells: insulin activation of type 1 phosphatase.
Olivier, A. R., Ballou, L. M., & Thomas, G. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.13.4720 · Cited by 68 · see citing works
Mn2(+)-binding properties of a recombinant protein-tyrosine kinase derived from the human insulin receptor.
Wente, S. R., Villalba, M., Schramm, V. L., & Rosen, O. M. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.7.2805 · Cited by 35 · see citing works
The nature of the decreased activity of glycogen synthase phosphatase in the liver of the adrenalectomized starved rat
Bollen, M., Doperé, F., Goris, J., et al. (1984) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1984.tb08430.x · Cited by 21 · see citing works

Flagged first, then by citations

Research works printed but not linked: 7

Myers, M. G. J., Backer, J. M., Sun, X. J., Shoelson, S., Hu, P., Schlessinger, J., Yoakim, M., Schaffhausen, B. & White, M. F. (1992) Proc. Natl. Acad. Sci. USA 89, 10350-10354.
Lee, C. H., Li, W., Nishimura, R., Zhou, M., Batzer, A. G., Myers, M. G., Jr., White, M. F., Schlessinger, J. & Skolnik, E. Y. (1993) Proc. Natl. Acad. Sci. USA 90, 11713-11717.
Hotamisligil, G. S., Murray, D. L., Choy, L. N. & Spiegelman, B. M. (1994) Proc. Natl. Acad. Sci. USA 91, 4854-4858.
Pierce, S. B. & Kimelman, D. (1995) Development (Cambridge, U.K.) 121, 755-765.
Eldar-Finkelman, H., Agrast, G. M., Foord, O., Fischer, E. H. & Krebs, E. G. (1996) Proc. Natl. Acad. Sci. USA 93, 10228-10233.
Wente, S. R., Villalba, M., Schramm, V. L. & Rosen, O. M. (1990) Proc. Natl. Acad. Sci. USA 87, 2805-2809.
Olivier, A. R., Ballou, L. M. & Thomas, G. (1988) Proc. Natl. Acad. Sci. USA 85, 4720-4724.

Sorted by citations

GSK-3: tricks of the trade for a multi-tasking kinase
Doble, B. W., & Woodgett, J. R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00384 · Cited by 2,084 · see citing works
Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases
Beurel, E., Grieco, S. F., & Jope, R. S. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.11.016 · Cited by 1,768 · see citing works
GSK3 takes centre stage more than 20 years after its discovery
FRAME, S., & COHEN, P. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3590001 · Cited by 1,433 · see citing works
Cinnamon improves glucose and lipids of people with type 2 diabetes
Khan, A., Safdar, M., Ali Khan, M. M., Khattak, K. N., & Anderson, R. A. (2003) · Diabetes Care · doi:10.2337/diacare.26.12.3215 · Cited by 981 · see citing works
Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling
SHEPHERD, P. R., WITHERS, D. J., & SIDDLE, K. (1998) · Biochemical Journal · doi:10.1042/bj3330471 · Cited by 953 · see citing works
Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1
Maurer, U., Charvet, C., Wagman, A. S., Dejardin, E., & Green, D. R. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.009 · Cited by 881 · see citing works
Phosphorylation of IRS proteins, insulin action, and insulin resistance
Boura-Halfon, S., & Zick, Y. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90437.2008 · Cited by 598 · see citing works
Selective Glycogen Synthase Kinase 3 Inhibitors Potentiate Insulin Activation of Glucose Transport and Utilization In Vitro and In Vivo
Ring, D. B., Johnson, K. W., Henriksen, E. J., Nuss, J. M., Goff, D., Kinnick, T. R., Ma, S. T., Reeder, J. W., Samuels, I., Slabiak, T., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.3.588 · Cited by 532 · see citing works
Proposed mechanisms for the induction of insulin resistance by oxidative stress
Bloch-Damti, A., & Bashan, N. (2005) · Antioxidants & Redox Signaling · doi:10.1089/ars.2005.7.1553 · Cited by 388 · see citing works
A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3-L1 adipocytes
Jarvill-Taylor, K. J., Anderson, R. A., & Graves, D. J. (2001) · Journal of the American College of Nutrition · doi:10.1080/07315724.2001.10719053 · Cited by 324 · see citing works
Glucocorticoid-induced insulin resistance in skeletal muscles: defects in insulin signalling and the effects of a selective glycogen synthase kinase-3 inhibitor
Ruzzin, J., Wagman, A. S., & Jensen, J. (2005) · Diabetologia · doi:10.1007/s00125-005-1886-0 · Cited by 243 · see citing works
5′-AMP-activated Protein Kinase Phosphorylates IRS-1 on Ser-789 in Mouse C2C12 Myotubes in Response to 5-Aminoimidazole-4-carboxamide Riboside
Jakobsen, S. N., Hardie, D. G., Morrice, N., & Tornqvist, H. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100483200 · Cited by 238 · see citing works
Inhibition of GSK-3 Selectively Reduces Glucose-6-Phosphatase and Phosphoenolpyruvate Carboxykinase Gene Expression
Lochhead, P. A., Coghlan, M., Rice, S. Q. J., & Sutherland, C. (2001) · Diabetes · doi:10.2337/diabetes.50.5.937 · Cited by 219 · see citing works
Inhibition of Glycogen Synthase Kinase 3 Improves Insulin Action and Glucose Metabolism in Human Skeletal Muscle
Nikoulina, S. E., Ciaraldi, T. P., Mudaliar, S., Carter, L., Johnson, K., & Henry, R. R. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2190 · Cited by 198 · see citing works
GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease
Gao, C., Hölscher, C., Liu, Y., & Li, L. (2012) · revneuro · doi:10.1515/rns.2011.061 · Cited by 164 · see citing works
Adipose-specific Expression, Phosphorylation of Ser794 in Insulin Receptor Substrate-1, and Activation in Diabetic Animals of Salt-inducible Kinase-2
Horike, N., Takemori, H., Katoh, Y., Doi, J., Min, L., Asano, T., Sun, X. J., Yamamoto, H., Kasayama, S., Muraoka, M., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211770200 · Cited by 161 · see citing works
The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction
Cohen, P. (1999) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1999.0399 · Cited by 158 · see citing works
Signalling through the insulin receptor
Whitehead, J. P., Clark, S. F., Ursø, B., & James, D. E. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)00079-4 · Cited by 130 · see citing works
Skeletal muscle insulin resistance in normoglycemic subjects with a strong family history of type 2 diabetes is associated with decreased insulin-stimulated insulin receptor substrate-1 tyrosine phosphorylation
Pratipanawatr, W., Pratipanawatr, T., Cusi, K., Berria, R., Adams, J. M., Jenkinson, C. P., Maezono, K., DeFronzo, R. A., & Mandarino, L. J. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2572 · Cited by 118 · see citing works
Modulation of muscle insulin resistance by selective inhibition of GSK-3 in Zucker diabetic fatty rats
Henriksen, E. J., Kinnick, T. R., Teachey, M. K., O'Keefe, M. P., Ring, D., Johnson, K. W., & Harrison, S. D. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00346.2002 · Cited by 108 · see citing works
In Vivo Phosphorylation of Insulin Receptor Substrate 1 at Serine 789 by a Novel Serine Kinase in Insulin-resistant Rodents
Qiao, L.-Y., Zhande, R., Jetton, T. L., Zhou, G., & Sun, X. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201494200 · Cited by 104 · see citing works
Development of inhibitors targeting glycogen synthase kinase-3β for human diseases: Strategies to improve selectivity
Wei, J., Wang, J., Zhang, J., Yang, J., Wang, G., & Wang, Y. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114301 · Cited by 42 · see citing works
Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity
Xian, L., Hou, S., Huang, Z., Tang, A., Shi, P., Wang, Q., Song, A., Jiang, S., Lin, Z., Guo, S., et al. (2015) · Aging · doi:10.18632/aging.100725 · Cited by 31 · see citing works

Insulin receptor substrates 1 and 2 but not Shc can activate the insulin receptor independent of insulin and induce proliferation in CHO-IR cells
Nießen, M., Jaschinski, F., Item, F., et al. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.11.015 · Cited by 8 · see citing works
AUTHOR COPY ONLY Glycogen synthase kinase 3b mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate 1
Leng, S.-H., Zhang, W., Zheng, Y., Liberman, Z., Rhodes, C. J., Eldar-Finkelman, H., & Sun, X. (2010)
Self-citation
Grb10 Inhibits Insulin-stimulated Insulin Receptor Substrate (IRS)-Phosphatidylinositol 3-Kinase/Akt Signaling Pathway by Disrupting the Association of IRS-1/IRS-2 with the Insulin Receptor
Wick, K. R., Werner, E. D., Langlais, P. R., Ramos, F. J., Dong, L., Shoelson, S. E., & Liu, F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208518200 · Cited by 119 · see citing works
Untitled work
(2006) · doi:10.1016/j.tem.2006.01.005 · Cited by 256 · see citing works
Insulin receptor substrate 1 and 2 (IRS1 and IRS2): what a tangled web we weave
Waters, S. B., & Pessin, J. E. (1996) · Trends in Cell Biology · doi:10.1016/0962-8924(96)81024-5 · Cited by 67 · see citing works

Authors: Eldar-Finkelman, H., & Krebs, E. G.
Affiliations: University of Washington (US)
Corresponding author: Krebs, Edwin G.
ORCID: Eldar-Finkelman, Hagit
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1997-09-02
Volume: 94
Issue: 18
Pages: 9660-9664
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.94.18.9660
PMC: PMC23245
OpenAlex: W2049875806
Cited by: 319
References: 39
Citations by year: 2026: 4 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 10 · 2017: 7 · 2016: 9 · 2015: 7 · 2014: 10 · 2013: 10 · 2012: 8
FWCI: 4.50
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Muscular Dystrophy Association
Washington State University
University of Washington
National Institutes of Health (5r01dk042528-10)
National Institute of Diabetes and Digestive and Kidney Diseases (DK42528)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Keywords: IRS-1, glycogen synthase kinase-3, serine phosphorylation, insulin receptor tyrosine kinase, insulin signaling, insulin resistance, IRS-1 tyrosine phosphorylation, SH2 domain proteins, kinase inhibition
MeSH terms: Animals, Cricetinae, Insulin, Phosphoproteins, Phosphorylation, Recombinant Proteins, Substrate Specificity, CHO Cells, Calcium-Calmodulin-Dependent Protein Kinases, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, Insulin Receptor Substrate Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks