Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 25 June 1993:
Vol. 260. no. 5116, pp. 1953 - 1955
DOI: 10.1126/science.8316835
Prev | Table of Contents | Next

Articles

Science, Vol 260, Issue 5116, 1953-1955
Copyright © 1993 by American Association for the Advancement of Science

articles

The function of GRB2 in linking the insulin receptor to Ras signaling pathways

EY Skolnik, A Batzer, N Li, CH Lee, E Lowenstein, M Mohammadi, B Margolis, and J Schlessinger

Department of Pharmacology, New York University Medical Center, NY 10016.

Insulin-induced activation of extracellular signal-regulated kinases [ERKs, also known as mitogen-activated protein (MAP) kinases] is mediated by Ras. Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. Moreover, a dominant negative form of Ras (with Ser17 substituted with Asn) blocked insulin-induced activation of ERKs in cells that overexpressed GRB2. GRB2 overexpression led to increased formation of a complex between the guanine nucleotide-releasing factor Sos (the product of the mammalian homolog of son of sevenless gene) and GRB2. In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Distinct roles for Crk adaptor isoforms in actin reorganization induced by extracellular signals.
S. Antoku and B. J. Mayer (2009)
J. Cell Sci. 122, 4228-4238
   Abstract »    Full Text »    PDF »
SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans.
E. Neumann-Haefelin, W. Qi, E. Finkbeiner, G. Walz, R. Baumeister, and M. Hertweck (2008)
Genes & Dev. 22, 2721-2735
   Abstract »    Full Text »    PDF »
Regulation of Neurogenesis and Epidermal Growth Factor Receptor Signaling by the Insulin Receptor/Target of Rapamycin Pathway in Drosophila.
H. McNeill, G. M. Craig, and J. M. Bateman (2008)
Genetics 179, 843-853
   Abstract »    Full Text »    PDF »
53BP2S, Interacting with Insulin Receptor Substrates, Modulates Insulin Signaling.
F. Hakuno, S. Kurihara, R. T. Watson, J. E. Pessin, and S.-I. Takahashi (2007)
J. Biol. Chem. 282, 37747-37758
   Abstract »    Full Text »    PDF »
Oxygen Tension Regulates the Stability of Insulin Receptor Substrate-1 (IRS-1) through Caspase-mediated Cleavage.
S. G. Kang, A. L. Brown, and J. H. Chung (2007)
J. Biol. Chem. 282, 6090-6097
   Abstract »    Full Text »    PDF »
Insulin Resistance and Atherosclerosis.
J. Nigro, N. Osman, A. M. Dart, and P. J. Little (2006)
Endocr. Rev. 27, 242-259
   Abstract »    Full Text »    PDF »
Differential Activation of Insulin Receptor Isoforms by Insulin-Like Growth Factors Is Determined by the C Domain.
A. Denley, G. V. Brierley, J. M. Carroll, A. Lindenberg, G. W. Booker, L. J. Cosgrove, J. C. Wallace, B. E. Forbes, and C. T. Roberts Jr. (2006)
Endocrinology 147, 1029-1036
   Abstract »    Full Text »    PDF »
RACK1 Recruits STAT3 Specifically to Insulin and Insulin-Like Growth Factor 1 Receptors for Activation, Which Is Important for Regulating Anchorage-Independent Growth.
W. Zhang, C. S. Zong, U. Hermanto, P. Lopez-Bergami, Z. Ronai, and L.-H. Wang (2006)
Mol. Cell. Biol. 26, 413-424
   Abstract »    Full Text »    PDF »
Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family.
J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner (2005)
Endocr. Rev. 26, 525-582
   Abstract »    Full Text »    PDF »
Inhibition of Microsomal Triglyceride Transfer Protein Expression and Apolipoprotein B100 Secretion by the Citrus Flavonoid Naringenin and by Insulin Involves Activation of the Mitogen-Activated Protein Kinase Pathway in Hepatocytes.
E. M. Allister, N. M. Borradaile, J. Y. Edwards, and M. W. Huff (2005)
Diabetes 54, 1676-1683
   Abstract »    Full Text »    PDF »
Phosphorylation of p66Shc and forkhead proteins mediates A{beta} toxicity.
W. W. Smith, D. D. Norton, M. Gorospe, H. Jiang, S. Nemoto, N. J. Holbrook, T. Finkel, and J. W. Kusiak (2005)
J. Cell Biol. 169, 331-339
   Abstract »    Full Text »    PDF »
Homocysteine thiolactone inhibits insulin-stimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation.
S Najib and V Sanchez-Margalet (2005)
J. Mol. Endocrinol. 34, 119-126
   Abstract »    Full Text »    PDF »
Diabetes Induces p66shc Gene Expression in Human Peripheral Blood Mononuclear Cells: Relationship to Oxidative Stress.
E. Pagnin, G. Fadini, R. de Toni, A. Tiengo, L. Calo, and A. Avogaro (2005)
J. Clin. Endocrinol. Metab. 90, 1130-1136
   Abstract »    Full Text »    PDF »
Insulin potentiates AVP-induced AQP2 expression in cultured renal collecting duct principal cells.
M. Bustamante, U. Hasler, O. Kotova, A. V. Chibalin, D. Mordasini, M. Rousselot, A. Vandewalle, P.-Y. Martin, and E. Feraille (2005)
Am J Physiol Renal Physiol 288, F334-F344
   Abstract »    Full Text »    PDF »
Mouse Models of Insulin Resistance.
A. NANDI, Y. KITAMURA, C. R. KAHN, and D. ACCILI (2004)
Physiol Rev 84, 623-647
   Abstract »    Full Text »    PDF »
The Cross-Talk between Angiotensin and Insulin Differentially Affects Phosphatidylinositol 3-Kinase- and Mitogen-Activated Protein Kinase-Mediated Signaling in Rat Heart: Implications for Insulin Resistance.
J. B. C. Carvalheira, V. C. Calegari, H. G. Zecchin, W. Nadruz Jr., R. B. Guimaraes, E. B. Ribeiro, K. G. Franchini, L. A. Velloso, and M. J. A. Saad (2003)
Endocrinology 144, 5604-5614
   Abstract »    Full Text »    PDF »
Ras Participates in CpG Oligodeoxynucleotide Signaling through Association with Toll-like Receptor 9 and Promotion of Interleukin-1 Receptor-associated Kinase/Tumor Necrosis Factor Receptor-associated Factor 6 Complex Formation in Macrophages.
H. Xu, H. An, Y. Yu, M. Zhang, R. Qi, and X. Cao (2003)
J. Biol. Chem. 278, 36334-36340
   Abstract »    Full Text »    PDF »
Morphine Induces Desensitization of Insulin Receptor Signaling.
Y. Li, S. Eitan, J. Wu, C. J. Evans, B. Kieffer, X. Sun, and R. D. Polakiewicz (2003)
Mol. Cell. Biol. 23, 6255-6266
   Abstract »    Full Text »    PDF »
Ethanol Impairs Insulin-stimulated Neuronal Survival in the Developing Brain: ROLE OF PTEN PHOSPHATASE.
J. Xu, J. E. Yeon, H. Chang, G. Tison, G. J. Chen, J. Wands, and S. de la Monte (2003)
J. Biol. Chem. 278, 26929-26937
   Abstract »    Full Text »    PDF »
Matrix-independent Activation of Phosphatidylinositol 3-Kinase, Stat3, and Cyclin A-associated Cdk2 Is Essential for Anchorage-independent Growth of v-Ros-transformed Chicken Embryo Fibroblasts.
S. Uttamsingh, C. S. Zong, and L.-H. Wang (2003)
J. Biol. Chem. 278, 18798-18810
   Abstract »    Full Text »    PDF »
Novel Signal Transduction Pathway for Luteinizing Hormone and Its Interaction with Insulin: Activation of Janus Kinase/Signal Transducer and Activator of Transcription and Phosphoinositol 3-Kinase/Akt Pathways.
C. R. O. Carvalho, J. B. C. Carvalheira, M. H. M. Lima, S. F. Zimmerman, L. C. Caperuto, A. Amanso, A. L. Gasparetti, V. Meneghetti, L. F. Zimmerman, L. A. Velloso, et al. (2003)
Endocrinology 144, 638-647
   Abstract »    Full Text »    PDF »
Insulin-like Growth Factor I-mediated Protection from Rapamycin-induced Apoptosis Is Independent of Ras-Erk1-Erk2 and Phosphatidylinositol 3'-Kinase-Akt Signaling Pathways.
K. N. Thimmaiah, J. Easton, S. Huang, K. A. Veverka, G. S. Germain, F. C. Harwood, and P. J. Houghton (2003)
Cancer Res. 63, 364-374
   Abstract »    Full Text »    PDF »
Affinity with Raf is sufficient for Ras to efficiently induce rat mammary carcinomas.
D. R. McFarlin, M. J. Lindstrom, and M. N. Gould (2003)
Carcinogenesis 24, 99-105
   Abstract »    Full Text »    PDF »
The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP3 levels.
S. Oldham, H. Stocker, M. Laffargue, F. Wittwer, M. Wymann, and E. Hafen (2002)
Development 129, 4103-4109
   Abstract »    Full Text »    PDF »
A Randomized Phase II and Pharmacokinetic Study of the Antisense Oligonucleotides ISIS 3521 and ISIS 5132 in Patients with Hormone-refractory Prostate Cancer.
A. W. Tolcher, L. Reyno, P. M. Venner, S. D. Ernst, M. Moore, R. S. Geary, K. Chi, S. Hall, W. Walsh, A. Dorr, et al. (2002)
Clin. Cancer Res. 8, 2530-2535
   Abstract »    Full Text »    PDF »
TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways.
J. M.-Y. Ho, M. H.-H. Nguyen, J. K. Dierov, K. M. Badger, B. K. Beattie, P. Tartaro, R. Haq, B. W. Zanke, M. P. Carroll, and D. L. Barber (2002)
Blood 100, 1438-1448
   Abstract »    Full Text »    PDF »
In Vivo Phosphorylation of Insulin Receptor Substrate 1 at Serine 789 by a Novel Serine Kinase in Insulin-resistant Rodents.
L.-y. Qiao, R. Zhande, T. L. Jetton, G. Zhou, and X. J. Sun (2002)
J. Biol. Chem. 277, 26530-26539
   Abstract »    Full Text »    PDF »
Augmentation effect of postprandial hyperinsulinaemia on growth of human hepatocellular carcinoma.
K Saito, S Inoue, T Saito, S Kiso, N Ito, S Tamura, H Watanabe, H Takeda, H Misawa, H Togashi, et al. (2002)
Gut 51, 100-104
   Abstract »    Full Text »    PDF »
Guanine nucleotide exchange factors for Rho GTPases: turning on the switch.
A. Schmidt and A. Hall (2002)
Genes & Dev. 16, 1587-1609
   Full Text »    PDF »
RACK1, an Insulin-Like Growth Factor I (IGF-I) Receptor-Interacting Protein, Modulates IGF-I-Dependent Integrin Signaling and Promotes Cell Spreading and Contact with Extracellular Matrix.
U. Hermanto, C. S. Zong, W. Li, and L.-H. Wang (2002)
Mol. Cell. Biol. 22, 2345-2365
   Abstract »    Full Text »    PDF »
Investigation of the GRB2, GRB7, and CSH1 genes as candidates for the Silver-Russell syndrome (SRS) on chromosome 17q.
M P Hitchins, S Abu-Amero, S Apostolidou, D Monk, P Stanier, M A Preece, and G E Moore (2002)
J. Med. Genet. 39, e13-13
   Full Text »    PDF »
c-Jun N-terminal Kinase Specifically Phosphorylates p66ShcA at Serine 36 in Response to Ultraviolet Irradiation.
S. Le, T. J. Connors, and A. C. Maroney (2001)
J. Biol. Chem. 276, 48332-48336
   Abstract »    Full Text »    PDF »
Silver-Russell syndrome: a dissection of the genetic aetiology and candidate chromosomal regions.
M. P Hitchins, P. Stanier, M. A Preece, and G. E Moore (2001)
J. Med. Genet. 38, 810-819
   Abstract »    Full Text »    PDF »
Inhibition of Mitogen-activated Protein Kinase Kinase Selectively Inhibits Cell Proliferation in Human Breast Cancer Cells Displaying Enhanced Insulin-like Growth Factor I-mediated Mitogen-activated Protein Kinase Activation.
U. Hermanto, C. S. Zong, and L.-H. Wang (2000)
Cell Growth Differ. 11, 655-664
   Abstract »    Full Text »
Insulin-Activated Protein Kinase Cbeta Bypasses Ras and Stimulates Mitogen-Activated Protein Kinase Activity and Cell Proliferation in Muscle Cells.
P. Formisano, F. Oriente, F. Fiory, M. Caruso, C. Miele, M. A. Maitan, F. Andreozzi, G. Vigliotta, G. Condorelli, and F. Beguinot (2000)
Mol. Cell. Biol. 20, 6323-6333
   Abstract »    Full Text »
Coupling of Gab1 to C-Met, Grb2, and Shp2 Mediates Biological Responses.
U. Schaeper, N. H. Gehring, K. P. Fuchs, M. Sachs, B. Kempkes, and W. Birchmeier (2000)
J. Cell Biol. 149, 1419-1432
   Abstract »    Full Text »    PDF »
The Differential Effects of pp120 (Ceacam 1) on the Mitogenic Action of Insulin and Insulin-Like Growth Factor 1 Are Regulated by the Nonconserved Tyrosine 1316 in the Insulin Receptor.
P. Soni, M. Lakkis, M. N. Poy, M. A. Fernström, and S. M. Najjar (2000)
Mol. Cell. Biol. 20, 3896-3905
   Abstract »    Full Text »
A Phase I Trial of c-Raf Kinase Antisense Oligonucleotide ISIS 5132 Administered as a Continuous Intravenous Infusion in Patients with Advanced Cancer.
C. C. Cunningham, J. T. Holmlund, J. H. Schiller, R. S. Geary, T. J. Kwoh, A. Dorr, and J. Nemunaitis (2000)
Clin. Cancer Res. 6, 1626-1631
   Abstract »    Full Text »    PDF »
Brain Insulin Receptor Causes Activity-Dependent Current Suppression in the Olfactory Bulb Through Multiple Phosphorylation of Kv1.3.
D. A. Fadool, K. Tucker, J. J. Phillips, and J. A. Simmen (2000)
J Neurophysiol 83, 2332-2348
   Abstract »    Full Text »    PDF »
Interleukin-4 Mediates Cell Growth Inhibition through Activation of Stat1.
T. L.-Y. Chang, X. Peng, and X.-Y. Fu (2000)
J. Biol. Chem. 275, 10212-10217
   Abstract »    Full Text »    PDF »
Tyrosine Dephosphorylation and Deactivation of Insulin Receptor Substrate-1 by Protein-tyrosine Phosphatase 1B. POSSIBLE FACILITATION BY THE FORMATION OF A TERNARY COMPLEX WITH THE GRB2 ADAPTOR PROTEIN.
B. J. Goldstein, A. Bittner-Kowalczyk, M. F. White, and M. Harbeck (2000)
J. Biol. Chem. 275, 4283-4289
   Abstract »    Full Text »    PDF »
Effect of Contraction on Mitogen-activated Protein Kinase Signal Transduction in Skeletal Muscle. INVOLVEMENT OF THE MITOGEN- AND STRESS-ACTIVATED PROTEIN KINASE 1.
J. W. Ryder, R. Fahlman, H. Wallberg-Henriksson, D. R. Alessi, A. Krook, and J. R. Zierath (2000)
J. Biol. Chem. 275, 1457-1462
   Abstract »    Full Text »    PDF »
IRS-4 Mediates Protein Kinase B Signaling during Insulin Stimulation without Promoting Antiapoptosis.
T. Uchida, M. G. Myers Jr., and M. F. White (2000)
Mol. Cell. Biol. 20, 126-138
   Abstract »    Full Text »
Vinexin Forms a Signaling Complex with Sos and Modulates Epidermal Growth Factor-induced c-Jun N-terminal Kinase/Stress-activated Protein Kinase Activities.
M. Akamatsu, S.-i. Aota, A. Suwa, K. Ueda, T. Amachi, K. M. Yamada, S. K. Akiyama, and N. Kioka (1999)
J. Biol. Chem. 274, 35933-35937
   Abstract »    Full Text »    PDF »
Accelerated Mammary Tumor Development in Mutant Polyomavirus Middle T Transgenic Mice Expressing Elevated Levels of Either the Shc or Grb2 Adapter Protein.
M. J. Rauh, V. Blackmore, E. R. Andrechek, C. G. Tortorice, R. Daly, V. K.-M. Lai, T. Pawson, R. D. Cardiff, P. M. Siegel, and W. J. Muller (1999)
Mol. Cell. Biol. 19, 8169-8179
   Abstract »    Full Text »    PDF »
Cas Mediates Transcriptional Activation of the Serum Response Element by Src.
Y. Hakak and G. S. Martin (1999)
Mol. Cell. Biol. 19, 6953-6962
   Abstract »    Full Text »    PDF »
Role of the Src Homology 2 (SH2) Domain and C-Terminus Tyrosine Phosphorylation Sites of SH2-Containing Inositol Phosphatase (SHIP) in the Regulation of Insulin-Induced Mitogenesis.
T. Wada, T. Sasaoka, M. Ishiki, H. Hori, T. Haruta, H. Ishihara, and M. Kobayashi (1999)
Endocrinology 140, 4585-4594
   Abstract »    Full Text »
Insulin-induced Desensitization of Extracellular Signal-regulated Kinase Activation Results from an Inhibition of Raf Activity Independent of Ras Activation and Dissociation of the Grb2-SOS Complex.
R. V. Fucini, S. Okada, and J. E. Pessin (1999)
J. Biol. Chem. 274, 18651-18658
   Abstract »    Full Text »    PDF »
Vascular Endothelial Growth Factor Induces Activation and Subcellular Translocation of Focal Adhesion Kinase (p125FAK) in Cultured Rat Cardiac Myocytes.
N. Takahashi, Y. Seko, E. Noiri, K. Tobe, T. Kadowaki, H. Sabe, and Y. Yazaki (1999)
Circ. Res. 84, 1194-1202
   Abstract »    Full Text »    PDF »
Insulin-Like Growth Factor I Synergizes with Interleukin 4 for Hematopoietic Cell Proliferation Independent of Insulin Receptor Substrate Expression.
L. Soon, L. Flechner, J. S. Gutkind, L.-H. Wang, R. Baserga, J. H. Pierce, and W. Li (1999)
Mol. Cell. Biol. 19, 3816-3828
   Abstract »    Full Text »    PDF »
Pancreatic Glucagon-Like Peptide-1 Receptor Couples to Multiple G Proteins and Activates Mitogen-Activated Protein Kinase Pathways in Chinese Hamster Ovary Cells.
C. Montrose-Rafizadeh, P. Avdonin, M. J. Garant, B. D. Rodgers, S. Kole, H. Yang, M. A. Levine, W. Schwindinger, and M. Bernier (1999)
Endocrinology 140, 1132-1140
   Abstract »    Full Text »
Insulin-Like Growth Factor I Suppresses Parathyroid Hormone (PTH)/PTH-Related Protein Receptor Expression via a Mitogen-Activated Protein Kinase Pathway in UMR-106 Osteoblast-Like Cells.
T. Kawane and N. Horiuchi (1999)
Endocrinology 140, 871-879
   Abstract »    Full Text »
Shc Dominant Negative Disrupts Cell Cycle Progression in Both G0-G1 and G2-M of ErbB2-positive Breast Cancer Cells.
L. E. Stevenson, K. S. Ravichandran, and A. R. Frackelton Jr. (1999)
Cell Growth Differ. 10, 61-71
   Abstract »    Full Text »
Insulin Receptor Substrate 2 And Shc Play Different Roles In Insulin-like Growth Factor I Signaling.
B. Kim, H.-L. Cheng, B. Margolis, and E. L. Feldman (1998)
J. Biol. Chem. 273, 34543-34550
   Abstract »    Full Text »    PDF »
Differential Regulation of Insulin Receptor Substrate-2 and Mitogen-Activated Protein Kinase Tyrosine Phosphorylation by Phosphatidylinositol 3-Kinase Inhibitors in SH-SY5Y Human Neuroblastoma Cells.
B. Kim, P. S. Leventhal, M. F. White, and E. L. Feldman (1998)
Endocrinology 139, 4881-4889
   Abstract »    Full Text »    PDF »
Actin Filaments Facilitate Insulin Activation of the Src and Collagen Homologous/Mitogen-activated Protein Kinase Pathway Leading to DNA Synthesis and c-fos Expression.
T. Tsakiridis, A. Bergman, R. Somwar, C. Taha, K. Aktories, T. F. Cruz, A. Klip, and G. P. Downey (1998)
J. Biol. Chem. 273, 28322-28331
   Abstract »    Full Text »    PDF »
Reconstitution of Insulin Signaling Pathways in Rat 3Y1 Cells Lacking Insulin Receptor and Insulin Receptor Substrate-1. EVIDENCE THAT ACTIVATION OF Akt IS INSUFFICIENT FOR INSULIN-STIMULATED GLYCOGEN SYNTHESIS OR GLUCOSE UPTAKE IN RAT 3Y1 CELLS.
T. Imanaka, H. Hayashi, K. Kishi, L. Wang, K. Ishii, O. Hazeki, T. Katada, and Y. Ebina (1998)
J. Biol. Chem. 273, 25347-25355
   Abstract »    Full Text »    PDF »
Grb2 Forms an Inducible Protein Complex with CD28 through a Src Homology 3 Domain-Proline Interaction.
K. Okkenhaug and R. Rottapel (1998)
J. Biol. Chem. 273, 21194-21202
   Abstract »    Full Text »    PDF »
A Novel Insulin Receptor Substrate Protein, xIRS-u, Potentiates Insulin Signaling: Functional Importance of Its Pleckstrin Homology Domain.
N. Ohan, M. Bayaa, P. Kumar, L. Zhu, and X. J. Liu (1998)
Mol. Endocrinol. 12, 1086-1098
   Abstract »    Full Text »
Replacement of Tyrosine 1251 in the Carboxyl Terminus of the Insulin-like Growth Factor-I Receptor Disrupts the Actin Cytoskeleton and Inhibits Proliferation and Anchorage-independent Growth.
V. A. Blakesley, A. P. Koval, B. S. Stannard, A. Scrimgeour, and D. LeRoith (1998)
J. Biol. Chem. 273, 18411-18422
   Abstract »    Full Text »    PDF »
Growth Factor Receptor-Bound Protein 2 (Grb2) Association with Hemopoietic Specific Protein 1: Linkage Between Lck and Grb2.
Y. Takemoto, M. Furuta, M. Sato, P. R. Findell, W. Ramble, and Y. Hashimoto (1998)
J. Immunol. 161, 625-630
   Abstract »    Full Text »    PDF »
Binding of Shp2 Tyrosine Phosphatase to FRS2 Is Essential for Fibroblast Growth Factor-Induced PC12 Cell Differentiation.
Y. R. Hadari, H. Kouhara, I. Lax, and J. Schlessinger (1998)
Mol. Cell. Biol. 18, 3966-3973
   Abstract »    Full Text »
Interplay of the Proto-oncogene Proteins CrkL and CrkII in Insulin-like Growth Factor-I Receptor-mediated Signal Transduction.
A. P. Koval, M. Karas, Y. Zick, and D. LeRoith (1998)
J. Biol. Chem. 273, 14780-14787
   Abstract »    Full Text »    PDF »
Association of the Insulin Receptor with Phospholipase C-gamma (PLCgamma ) in 3T3-L1 Adipocytes Suggests a Role for PLCgamma in Metabolic Signaling by Insulin.
A. G. Kayali, J. Eichhorn, T. Haruta, A. J. Morris, J. G. Nelson, P. Vollenweider, J. M. Olefsky, and N. J. G. Webster (1998)
J. Biol. Chem. 273, 13808-13818
   Abstract »    Full Text »    PDF »
Insulin Receptor-mediated Dissociation of Grb2 from Sos Involves Phosphorylation of Sos by Kinase(s) Other than Extracellular Signal-regulated Kinase.
H. Zhao, S. Okada, J. E. Pessin, and G. A. Koretzky (1998)
J. Biol. Chem. 273, 12061-12067
   Abstract »    Full Text »    PDF »
Insulin-like Growth Factor-1 (IGF-1) Receptor-Insulin Receptor Substrate Complexes in the Uterus. ALTERED SIGNALING RESPONSE TO ESTRADIOL IN THE IGF-1m/m MOUSE.
R. G. Richards, M. P. Walker, J. Sebastian, and R. P. DiAugustine (1998)
J. Biol. Chem. 273, 11962-11969
   Abstract »    Full Text »    PDF »
Insulin Receptor Substrate (IRS) Proteins IRS-1 and IRS-2 Differential Signaling in the Insulin/Insulin-Like Growth Factor-I Pathways in Fetal Brown Adipocytes.
A. M. Valverde, M. Lorenzo, S. Pons, M. F. White, and M. Benito (1998)
Mol. Endocrinol. 12, 688-697
   Abstract »    Full Text »
Roles of the Complex Formation of SHPS-1 with SHP-2 in Insulin-stimulated Mitogen-activated Protein Kinase Activation.
T. Takada, T. Matozaki, H. Takeda, K. Fukunaga, T. Noguchi, Y. Fujioka, I. Okazaki, M. Tsuda, T. Yamao, F. Ochi, et al. (1998)
J. Biol. Chem. 273, 9234-9242
   Abstract »    Full Text »    PDF »
Anti-apoptotic Signaling by a Colony-stimulating Factor-1 Receptor/Insulin Receptor Chimera with a Juxtamembrane Deletion.
J. E. Boehm, O. V. Chaika, and R. E. Lewis (1998)
J. Biol. Chem. 273, 7169-7176
   Abstract »    Full Text »    PDF »
Intracellular Localization of Phosphatidylinositide 3-kinase and Insulin Receptor Substrate-1 in Adipocytes: Potential Involvement of a Membrane Skeleton.
S. F. Clark, S. Martin, A. J. Carozzi, M. M. Hill, and D. E. James (1998)
J. Cell Biol. 140, 1211-1225
   Abstract »    Full Text »    PDF »
Receptor-like Protein-tyrosine Phosphatase alpha  Specifically Inhibits Insulin-increased Prolactin Gene Expression.
K. K. Jacob, J. Sap, and F. M. Stanley (1998)
J. Biol. Chem. 273, 4800-4809
   Abstract »    Full Text »    PDF »
Ras-GRF Activates Ha-Ras, but Not N-Ras or K-Ras 4B, Protein in Vivo.
M. K. Jones and J. H. Jackson (1998)
J. Biol. Chem. 273, 1782-1787
   Abstract »    Full Text »    PDF »
Ligand-Independent GLUT4 Translocation Induced by Guanosine 5'-O-(3-Thiotriphosphate) Involves Tyrosine Phosphorylation.
T. Haruta, A. J. Morris, P. Vollenweider, J. G. Nelson, D. W. Rose, M. Mueckler, and J. M. Olefsky (1998)
Endocrinology 139, 358-364
   Abstract »    Full Text »    PDF »
Multiple Myeloma: Increasing Evidence for a Multistep Transformation Process.
M. Hallek, P. Leif Bergsagel, and K. C. Anderson (1998)
Blood 91, 3-21
   Full Text »    PDF »
Mitogenic Signaling of Insulin-like Growth Factor I in MCF-7 Human Breast Cancer Cells Requires Phosphatidylinositol 3-Kinase and Is Independent of Mitogen-activated Protein Kinase.
B. Dufourny, J. Alblas, H. A. A. M. van Teeffelen, F. M. A van Schaik, B. van der Burg, P. H. Steenbergh, and J. S. Sussenbach (1997)
J. Biol. Chem. 272, 31163-31171
   Abstract »    Full Text »    PDF »
Insulin and Epidermal Growth Factor Stimulate a Conformational Change in Rap1 and Dissociation of the CrkII-C3G Complex.
S. Okada and J. E. Pessin (1997)
J. Biol. Chem. 272, 28179-28182
   Abstract »    Full Text »    PDF »
Differential Signaling to Glycogen Synthesis by the Intracellular Domain of the Insulin versus the Insulin-like Growth Factor-1 Receptor. EVIDENCE FROM STUDIES OF TrkC-CHIMERAS.
H. E. Kalloo-Hosein, J. P. Whitehead, M. Soos, J. M. Tavare, K. Siddle, and S. O'Rahilly (1997)
J. Biol. Chem. 272, 24325-24332
   Abstract »    Full Text »    PDF »
Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action.
H. Eldar-Finkelman and E. G. Krebs (1997)
PNAS 94, 9660-9664
   Abstract »    Full Text »    PDF »
Differential Utilization of ShcA Tyrosine Residues and Functional Domains in the Transduction of Epidermal Growth Factor-induced Mitogen-activated Protein Kinase Activation in 293T Cells and Nerve Growth Factor-induced Neurite Outgrowth in PC12 Cells. IDENTIFICATION OF A NEW Grb2·Sos1 BINDING SITE.
D. Thomas and R. A. Bradshaw (1997)
J. Biol. Chem. 272, 22293-22299
   Abstract »    Full Text »    PDF »
Tyrosine Residues in the C-Terminal Domain of the Insulin-Like Growth Factor-I Receptor Mediate Mitogenic and Tumorigenic Signals.
D. L. Esposito, V. A. Blakesley, A. P. Koval, A. G. Scrimgeour, and D. LeRoith (1997)
Endocrinology 138, 2979-2988
   Abstract »    Full Text »    PDF »
Insulin Stimulates the Phosphorylation of the 66- and 52-Kilodalton Shc Isoforms by Distinct Pathways.
A. W. Kao, S. B. Waters, S. Okada, and J. E. Pessin (1997)
Endocrinology 138, 2474-2480
   Abstract »    Full Text »    PDF »
CSF-1 Receptor/Insulin Receptor Chimera Permits CSF-1-dependent Differentiation of 3T3-L1 Preadipocytes.
O. V. Chaika, N. Chaika, D. J. Volle, P. A. Wilden, S. J. Pirrucello, and R. E. Lewis (1997)
J. Biol. Chem. 272, 11968-11974
   Abstract »    Full Text »    PDF »
Erythropoietin and Interleukin-3 Activate Tyrosine Phosphorylation of CBL and Association With CRK Adaptor Proteins.
D. L. Barber, J. M. Mason, T. Fukazawa, K. A. Reedquist, B. J. Druker, H. Band, and A. D. D'Andrea (1997)
Blood 89, 3166-3174
   Abstract »    Full Text »    PDF »
Shc Interaction with Src Homology 2Domain Containing Inositol Phosphatase (SHIP) in Vivo Requires the Shc-Phosphotyrosine Binding Domain and Two Specific Phosphotyrosines on SHIP.
T. D. Lamkin, S. F. Walk, L. Liu, J. E. Damen, G. Krystal, and K. S. Ravichandran (1997)
J. Biol. Chem. 272, 10396-10401
   Abstract »    Full Text »    PDF »
Functional Importance of Shc Tyrosine 317on Insulin Signaling in Rat1 Fibroblasts Expressing Insulin Receptors.
H. Ishihara, T. Sasaoka, M. Ishiki, Y. Takata, T. Imamura, I. Usui, W. J. Langlois, T. Sawa, and M. Kobayashi (1997)
J. Biol. Chem. 272, 9581-9586
   Abstract »    Full Text »    PDF »
Antisense Repression of Proto-oncogene c-Cbl Enhances Activation of the JAK-STAT Pathway but Not the Ras Pathway in Epidermal Growth Factor Receptor Signaling.
H. Ueno, K. Sasaki, K. Miyagawa, H. Honda, K. Mitani, Y. Yazaki, and H. Hirai (1997)
J. Biol. Chem. 272, 8739-8743
   Abstract »    Full Text »    PDF »
Stat5 is a physiological substrate of the insulin receptor.
J. Chen, H. B. Sadowski, R. A. Kohanski, and L.-H. Wang (1997)
PNAS 94, 2295-2300
   Abstract »    Full Text »    PDF »
A Molecular Redox Switch on p21ras. STRUCTURAL BASIS FOR THE NITRIC OXIDE-p21ras INTERACTION.
HarryM. Lander, DavidP. Hajjar, BarbaraL. Hempstead, UroojA. Mirza, BrianT. Chait, S. Campbell, and LawrenceA. Quilliam (1997)
J. Biol. Chem. 272, 4323-4326
   Abstract »    Full Text »    PDF »
A Casein Kinase I Activity Is Constitutively Associated with Nck.
G. Lussier and L. Larose (1997)
J. Biol. Chem. 272, 2688-2694
   Abstract »    Full Text »    PDF »
High Affinity Binding of the Pleckstrin Homology Domain of mSos1 to Phosphatidylinositol (4,5)-Bisphosphate.
T. J. Kubiseski, Y. M. Chook, W. E. Parris, M. Rozakis-Adcock, and T. Pawson (1997)
J. Biol. Chem. 272, 1799-1804
   Abstract »    Full Text »    PDF »
Erythropoietin Activates Raf1 by an Shc-Independent Pathway in CTLL-EPO-R Cells.
D. L. Barber, C. N. Corless, K. Xia, T. M. Roberts, and A. D. D'Andrea (1997)
Blood 89, 55-64
   Abstract »    Full Text »    PDF »
Insulin Signaling and Its Regulation of System A Amino Acid Uptake in Cultured Rat Vascular Smooth Muscle Cells.
T. Obata, A. Kashiwagi, H. Maegawa, Y. Nishio, S. Ugi, H. Hidaka, and R. Kikkawa (1996)
Circ. Res. 79, 1167-1176
   Abstract »    Full Text »
Regulation of the Association of p120cbl with Grb2 in Jurkat T Cells.
JeraldA. Donovan, Y. Ota, WallaceY. Langdon, and LawrenceE. Samelson (1996)
J. Biol. Chem. 271, 26369-26374
   Abstract »    Full Text »    PDF »
Interactions between Src Homology (SH) 2/SH3 Adapter Proteins and the Guanylnucleotide Exchange Factor SOS Are Differentially Regulated by Insulin and Epidermal Growth Factor.
S. Okada and J. E. Pessin (1996)
J. Biol. Chem. 271, 25533-25538
   Abstract »    Full Text »    PDF »
Overexpression of Rad Inhibits Glucose Uptake in Cultured Muscle and Fat Cells.
J. S. Moyers, P. J. Bilan, C. Reynet, and C. R. Kahn (1996)
J. Biol. Chem. 271, 23111-23116
   Abstract »    Full Text »    PDF »
Insulin Activates a p21-activated Kinase in Muscle Cells via Phosphatidylinositol 3-Kinase.
T. Tsakiridis, C. Taha, S. Grinstein, and A. Klip (1996)
J. Biol. Chem. 271, 19664-19667
   Abstract »    Full Text »    PDF »
Protein-tyrosine Phosphatase 1B Is a Negative Regulator of Insulin- and Insulin-like Growth Factor-I-stimulated Signaling.
K. A. Kenner, E. Anyanwu, J. M. Olefsky, and J. Kusari (1996)
J. Biol. Chem. 271, 19810-19816
   Abstract »    Full Text »    PDF »
MAP Kinase Activation by Flow in Endothelial Cells: Role of ß1 Integrins and Tyrosine Kinases.
T. Ishida, T. E. Peterson, N. L. Kovach, and B. C. Berk (1996)
Circ. Res. 79, 310-316
   Abstract »    Full Text »
Insulin and Epidermal Growth Factor Receptors Regulate Distinct Pools of Grb2-SOS in the Control of Ras Activation.
S. B. Waters, D. Chen, A. W. Kao, S. Okada, K. H. Holt, and J. E. Pessin (1996)
J. Biol. Chem. 271, 18224-18230
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)