This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jhun, B H
Right arrow Articles by Olefsky, J M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jhun, B H
Right arrow Articles by Olefsky, J M

 Previous Article  |  Next Article 

Mol Cell Biol. 1994 November; 14(11): 7466-7475

Microinjection of the SH2 domain of the 85-kilodalton subunit of phosphatidylinositol 3-kinase inhibits insulin-induced DNA synthesis and c-fos expression.

B H Jhun, D W Rose, B L Seely, L Rameh, L Cantley, A R Saltiel and J M Olefsky

Department of Medicine, University of California, San Diego, La Jolla 92093.

ABSTRACT

We have investigated the functional role of the SH2 domain of the 85-kDa subunit (p85) of the phosphatidylinositol 3-kinase in the insulin signal transduction pathway. Microinjection of a bacterial fusion protein containing the N-terminal SH2 domain of p85 inhibited insulin- and other growth factor-induced DNA synthesis by 90% and c-fos protein expression by 80% in insulin-responsive rat fibroblasts. The specificity of the fusion protein was examined by in vitro precipitation experiments, which showed that the SH2 domain of p85 can independently associate with both insulin receptor substrate 1 and the insulin receptor itself in the absence of detectable binding to other phosphoproteins. The microinjection results were confirmed through the use of an affinity-purified antibody directed against p85, which gave the same phenotype. Additional studies were carried out in another cell line expressing mutant insulin receptors which lack the cytoplasmic tyrosine residues with which p85 interacts. Microinjection of the SH2 domain fusion protein also inhibited insulin signaling in these cells, suggesting that association of p85 with insulin receptor substrate 1 is a key element in insulin-mediated cell cycle progression. In addition, coinjection of purified p21ras protein with the p85 fusion protein or the antibody restored DNA synthesis, suggesting that ras function is either downstream or independent of p85 SH2 domain interaction.

Mol Cell Biol. 1994 November; 14(11): 7466-7475




This article has been cited by other articles:

  • Wu, D., Peng, F., Zhang, B., Ingram, A. J., Kelly, D. J., Gilbert, R. E., Gao, B., Krepinsky, J. C. (2009). PKC-{beta}1 Mediates Glucose-Induced Akt Activation and TGF-{beta}1 Upregulation in Mesangial Cells. J. Am. Soc. Nephrol. 20: 554-566 [Abstract] [Full Text]  
  • Bandyopadhyay, G. K., Yu, J. G., Ofrecio, J., Olefsky, J. M. (2005). Increased p85/55/50 Expression and Decreased Phosphotidylinositol 3-Kinase Activity in Insulin-Resistant Human Skeletal Muscle. Diabetes 54: 2351-2359 [Abstract] [Full Text]  
  • Krepinsky, J. C., Li, Y., Chang, Y., Liu, L., Peng, F., Wu, D., Tang, D., Scholey, J., Ingram, A. J. (2005). Akt Mediates Mechanical Strain-Induced Collagen Production by Mesangial Cells. J. Am. Soc. Nephrol. 16: 1661-1672 [Abstract] [Full Text]  
  • Nishi, M., Werner, E. D., Oh, B.-C., Frantz, J. D., Dhe-Paganon, S., Hansen, L., Lee, J., Shoelson, S. E. (2005). Kinase Activation through Dimerization by Human SH2-B. Mol. Cell. Biol. 25: 2607-2621 [Abstract] [Full Text]  
  • Goo, Y.-H., Na, S.-Y., Zhang, H., Xu, J., Hong, S., Cheong, J., Lee, S.-K., Lee, J. W. (2004). Interactions between Activating Signal Cointegrator-2 and the Tumor Suppressor Retinoblastoma in Androgen Receptor Transactivation. J. Biol. Chem. 279: 7131-7135 [Abstract] [Full Text]  
  • Ijuin, T., Takenawa, T. (2003). SKIP Negatively Regulates Insulin-Induced GLUT4 Translocation and Membrane Ruffle Formation. Mol. Cell. Biol. 23: 1209-1220 [Abstract] [Full Text]  
  • Kim, S.-W., Cheong, C., Sohn, Y.-C., Goo, Y.-H., Oh, W. J., Park, J. H., Joe, S. Y., Kang, H.-S., Kim, D.-K., Kee, C., Lee, J. W., Lee, H.-W. (2002). Multiple Developmental Defects Derived from Impaired Recruitment of ASC-2 to Nuclear Receptors in Mice: Implication for Posterior Lenticonus with Cataract. Mol. Cell. Biol. 22: 8409-8414 [Abstract] [Full Text]  
  • Tuma, P. L., Nyasae, L. K., Backer, J. M., Hubbard, A. L. (2001). Vps34p differentially regulates endocytosis from the apical and basolateral domains in polarized hepatic cells. JCB 154: 1197-1208 [Abstract] [Full Text]  
  • Ono, H., Katagiri, H., Funaki, M., Anai, M., Inukai, K., Fukushima, Y., Sakoda, H., Ogihara, T., Onishi, Y., Fujishiro, M., Kikuchi, M., Oka, Y., Asano, T. (2001). Regulation of Phosphoinositide Metabolism, Akt Phosphorylation, and Glucose Transport by PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10) in 3T3-L1 Adipocytes. Mol. Endocrinol. 15: 1411-1422 [Abstract] [Full Text]  
  • Page, K., Li, J., Wang, Y., Kartha, S., Pestell, R. G., Hershenson, M. B. (2000). Regulation of Cyclin D1 Expression and DNA Synthesis by Phosphatidylinositol 3-Kinase in Airway Smooth Muscle Cells. Am. J. Respir. Cell Mol. Bio. 23: 436-443 [Abstract] [Full Text]  
  • Singleton, J. R., Baker, B. L., Thorburn, A. (2000). Dexamethasone Inhibits Insulin-Like Growth Factor Signaling and Potentiates Myoblast Apoptosis. Endocrinology 141: 2945-2950 [Abstract] [Full Text]  
  • Lee, S.-K., Na, S.-Y., Jung, S.-Y., Choi, J.-E., Jhun, B. H., Cheong, J., Meltzer, P. S., Lee, Y. C., Lee, J. W. (2000). Activating Protein-1, Nuclear Factor-{kappa}B, and Serum Response Factor as Novel Target Molecules of the Cancer-Amplified Transcription Coactivator ASC-2. Mol. Endocrinol. 14: 915-925 [Abstract] [Full Text]  
  • Egawa, K., Nakashima, N., Sharma, P. M., Maegawa, H., Nagai, Y., Kashiwagi, A., Kikkawa, R., Olefsky, J. M. (2000). Persistent Activation of Phosphatidylinositol 3-Kinase Causes Insulin Resistance Due to Accelerated Insulin-Induced Insulin Receptor Substrate-1 Degradation in 3T3-L1 Adipocytes. Endocrinology 141: 1930-1935 [Abstract] [Full Text]  
  • Nakashima, N., Sharma, P. M., Imamura, T., Bookstein, R., Olefsky, J. M. (2000). The Tumor Suppressor PTEN Negatively Regulates Insulin Signaling in 3T3-L1 Adipocytes. J. Biol. Chem. 275: 12889-12895 [Abstract] [Full Text]  
  • Desbois-Mouthon, C., Cadoret, A., Blivet-Van Eggelpoel, M.-J., Bertrand, F., Caron, M., Atfi, A., Cherqui, G., Capeau, J. (2000). Insulin-Mediated Cell Proliferation and Survival Involve Inhibition of c-Jun N-terminal Kinases through a Phosphatidylinositol 3-Kinase- and Mitogen-Activated Protein Kinase Phosphatase-1-Dependent Pathway. Endocrinology 141: 922-931 [Abstract] [Full Text]  
  • Hooshmand-Rad, R, Hajkova, L, Klint, P, Karlsson, R, Vanhaesebroeck, B, Claesson-Welsh, L, Heldin, C. (2000). The PI 3-kinase isoforms p110(alpha) and p110(beta) have differential roles in PDGF- and insulin-mediated signaling. J. Cell Sci. 113: 207-214 [Abstract]  
  • Band, C. J., Mounier, C., Posner, B. I. (1999). Epidermal Growth Factor and Insulin-Induced Deoxyribonucleic Acid Synthesis in Primary Rat Hepatocytes Is Phosphatidylinositol 3-Kinase Dependent and Dissociated from Protooncogene Induction. Endocrinology 140: 5626-5634 [Abstract] [Full Text]  
  • Lee, S.-K., Anzick, S. L., Choi, J.-E., Bubendorf, L., Guan, X.-Y., Jung, Y.-K., Kallioniemi, O. P., Kononen, J., Trent, J. M., Azorsa, D., Jhun, B.-H., Cheong, J. H., Lee, Y. C., Meltzer, P. S., Lee, J. W. (1999). A Nuclear Factor, ASC-2, as a Cancer-amplified Transcriptional Coactivator Essential for Ligand-dependent Transactivation by Nuclear Receptors in Vivo. J. Biol. Chem. 274: 34283-34293 [Abstract] [Full Text]  
  • Wada, T., Sasaoka, T., Ishiki, M., Hori, H., Haruta, T., Ishihara, H., Kobayashi, M. (1999). 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. Endocrinology 140: 4585-4594 [Abstract] [Full Text]  
  • Na, S.-Y., Choi, J.-E., Kim, H.-J., Jhun, B. H., Lee, Y.-C., Lee, J. W. (1999). Bcl3, an Ikappa B Protein, Stimulates Activating Protein-1 Transactivation and Cellular Proliferation. J. Biol. Chem. 274: 28491-28496 [Abstract] [Full Text]  
  • Cass, L. A., Summers, S. A., Prendergast, G. V., Backer, J. M., Birnbaum, M. J., Meinkoth, J. L. (1999). Protein Kinase A-Dependent and -Independent Signaling Pathways Contribute to Cyclic AMP-Stimulated Proliferation. Mol. Cell. Biol. 19: 5882-5891 [Abstract] [Full Text]  
  • Kim, H.-J., Yi, J.-Y., Sung, H.-S., Moore, D. D., Jhun, B. H., Lee, Y. C., Lee, J. W. (1999). Activating Signal Cointegrator 1, a Novel Transcription Coactivator of Nuclear Receptors, and Its Cytosolic Localization under Conditions of Serum Deprivation. Mol. Cell. Biol. 19: 6323-6332 [Abstract] [Full Text]  
  • Gillham, H., Golding, M. C.H.M., Pepperkok, R., Gullick, W. J. (1999). Intracellular Movement of Green Fluorescent Protein-Tagged Phosphatidylinositol 3-Kinase in Response to Growth Factor Receptor Signaling. JCB 146: 869-880 [Abstract] [Full Text]  
  • Sasaoka, T., Wada, T., Ishihara, H., Takata, Y., Haruta, T., Usui, I., Ishiki, M., Kobayashi, M. (1999). Synergistic Role of the Phosphatidylinositol 3-Kinase and Mitogen-Activated Protein Kinase Cascade in the Regulation of Insulin Receptor Trafficking. Endocrinology 140: 3826-3834 [Abstract] [Full Text]  
  • DIXON, R., BRUNSKILL, N. J. (1999). Activation of Mitogenic Pathways by Albumin in Kidney Proximal Tubule Epithelial Cells: Implications for the Pathophysiology of ProteinuricStates. J. Am. Soc. Nephrol. 10: 1487-1497 [Abstract] [Full Text]  
  • Egawa, K., Sharma, P. M., Nakashima, N., Huang, Y., Huver, E., Boss, G. R., Olefsky, J. M. (1999). Membrane-targeted Phosphatidylinositol 3-Kinase Mimics Insulin Actions and Induces a State of Cellular Insulin Resistance. J. Biol. Chem. 274: 14306-14314 [Abstract] [Full Text]  
  • Vollenweider, P., Clodi, M., Martin, S. S., Imamura, T., Kavanaugh, W. M., Olefsky, J. M. (1999). An SH2 Domain-Containing 5' Inositolphosphatase Inhibits Insulin-Induced GLUT4 Translocation and Growth Factor-Induced Actin Filament Rearrangement. Mol. Cell. Biol. 19: 1081-1091 [Abstract] [Full Text]  
  • Takuwa, N., Fukui, Y., Takuwa, Y. (1999). Cyclin D1 Expression Mediated by Phosphatidylinositol 3-Kinase through mTOR-p70S6K-Independent Signaling in Growth Factor-Stimulated NIH 3T3 Fibroblasts. Mol. Cell. Biol. 19: 1346-1358 [Abstract] [Full Text]  
  • Bavelloni, A, Santi, S, Sirri, A, Riccio, M, Faenza, I, Zini, N, Cecchi, S, Ferri, A, Auron, P, Maraldi, N., Marmiroli, S (1999). Phosphatidylinositol 3-kinase translocation to the nucleus is induced by interleukin 1 and prevented by mutation of interleukin 1 receptor in human osteosarcoma Saos-2 cells. J. Cell Sci. 112: 631-640 [Abstract]  
  • Siddhanta, U., McIlroy, J., Shah, A., Zhang, Y., Backer, J. M. (1998). Distinct Roles for the p110{alpha} and hVPS34 Phosphatidylinositol 3'-Kinases in Vesicular Trafficking, Regulation of the Actin Cytoskeleton, and Mitogenesis. JCB 143: 1647-1659 [Abstract] [Full Text]  
  • Roche, S., Downward, J., Raynal, P., Courtneidge, S. A. (1998). A Function for Phosphatidylinositol 3-Kinase beta  (p85alpha -p110beta ) in Fibroblasts during Mitogenesis: Requirement for Insulin- and Lysophosphatidic Acid-Mediated Signal Transduction. Mol. Cell. Biol. 18: 7119-7129 [Abstract] [Full Text]  
  • Clodi, M., Vollenweider, P., Klarlund, J., Nakashima, N., Martin, S., Czech, M. P., Olefsky, J. M. (1998). Effects of General Receptor for Phosphoinositides 1 on Insulin and Insulin-Like Growth Factor I-Induced Cytoskeletal Rearrangement, Glucose Transporter-4 Translocation, and Deoxyribonucleic Acid Synthesis. Endocrinology 139: 4984-4990 [Abstract] [Full Text]  
  • Imanaka, T., Hayashi, H., Kishi, K., Wang, L., Ishii, K., Hazeki, O., Katada, T., Ebina, Y. (1998). 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. J. Biol. Chem. 273: 25347-25355 [Abstract] [Full Text]  
  • Lei, S., Dryden, W. F., Smith, P. A. (1998). Involvement of Ras/MAP Kinase in the Regulation of Ca2+ Channels in Adult Bullfrog Sympathetic Neurons by Nerve Growth Factor. J. Neurophysiol. 80: 1352-1361 [Abstract] [Full Text]  
  • Sharma, P. M., Egawa, K., Huang, Y., Martin, J. L., Huvar, I., Boss, G. R., Olefsky, J. M. (1998). Inhibition of Phosphatidylinositol 3-Kinase Activity by Adenovirus-mediated Gene Transfer and Its Effect on Insulin Action. J. Biol. Chem. 273: 18528-18537 [Abstract] [Full Text]  
  • Kayali, A. G., Eichhorn, J., Haruta, T., Morris, A. J., Nelson, J. G., Vollenweider, P., Olefsky, J. M., Webster, N. J. G. (1998). Association of the Insulin Receptor with Phospholipase C-gamma (PLCgamma ) in 3T3-L1 Adipocytes Suggests a Role for PLCgamma in Metabolic Signaling by Insulin. J. Biol. Chem. 273: 13808-13818 [Abstract] [Full Text]  
  • He, W., Rose, D. W., Olefsky, J. M., Gustafson, T. A. (1998). Grb10 Interacts Differentially with the Insulin Receptor, Insulin-like Growth Factor I Receptor, and Epidermal Growth Factor Receptor via the Grb10 Src Homology 2 (SH2) Domain and a Second Novel Domain Located between the Pleckstrin Homology and SH2 Domains. J. Biol. Chem. 273: 6860-6867 [Abstract] [Full Text]  
  • Haruta, T., Morris, A. J., Vollenweider, P., Nelson, J. G., Rose, D. W., Mueckler, M., Olefsky, J. M. (1998). Ligand-Independent GLUT4 Translocation Induced by Guanosine 5'-O-(3-Thiotriphosphate) Involves Tyrosine Phosphorylation. Endocrinology 139: 358-364 [Abstract] [Full Text]  
  • Reddy, S. A. G., Huang, J. H., Liao, W. S.-L. (1997). Phosphatidylinositol 3-Kinase in Interleukin 1 Signaling. PHYSICAL INTERACTION WITH THE INTERLEUKIN 1 RECEPTOR AND REQUIREMENT IN NFkappa B AND AP-1 ACTIVATION. J. Biol. Chem. 272: 29167-29173 [Abstract] [Full Text]  
  • Waters, S. B., D'Auria, M., Martin, S. S., Nguyen, C., Kozma, L. M., Luskey, K. L. (1997). The Amino Terminus of Insulin-responsive Aminopeptidase Causes Glut4 Translocation in 3T3-L1 Adipocytes. J. Biol. Chem. 272: 23323-23327 [Abstract] [Full Text]  
  • Giorgino, F., Pedrini, M. T., Matera, L., Smith, R. J. (1997). Specific Increase in p85alpha Expression in Response to Dexamethasone Is Associated with Inhibition of Insulin-like Growth Factor-I Stimulated Phosphatidylinositol 3-Kinase Activity in Cultured Muscle Cells. J. Biol. Chem. 272: 7455-7463 [Abstract] [Full Text]  
  • Huang, C., Schmid, P. C., Ma, W.-Y., Schmid, H. H.O., Dong, Z. (1997). Phosphatidylinositol-3 Kinase Is Necessary for 12-O-Tetradecanoylphorbol-13-acetate-induced Cell Transformation and Activated Protein 1Activation. J. Biol. Chem. 272: 4187-4194 [Abstract] [Full Text]  
  • Ojaniemi, M., Martin, S. S., Dolfi, F., Olefsky, J. M., Vuori, K. (1997). The Proto-oncogene Product p120cbl Links c-Src and Phosphatidylinositol 3'-Kinase to the Integrin Signaling Pathway. J. Biol. Chem. 272: 3780-3787 [Abstract] [Full Text]  
  • O'Neill, T. J., Rose, D. W., Pillay, T. S., Hotta, K., Olefsky, J. M., Gustafson, T. A. (1996). Interaction of a GRB-IR Splice Variant (a Human GRB10 Homolog) with the Insulin and Insulin-like Growth Factor I Receptors. EVIDENCE FOR A ROLE IN MITOGENIC SIGNALING. J. Biol. Chem. 271: 22506-22513 [Abstract] [Full Text]  
  • Martin, S. S., Haruta, T., Morris, A. J., Klippel, A., Williams, L. T., Olefsky, J. M. (1996). Activated Phosphatidylinositol 3-Kinase Is Sufficient to Mediate Actin Rearrangement and GLUT4 Translocation in 3T3-L1 Adipocytes. J. Biol. Chem. 271: 17605-17608 [Abstract] [Full Text]  
  • Gabbay, R. A., Sutherland, C., Gnudi, L., Kahn, B. B., O'Brien, R. M., Granner, D. K., Flier, J. S. (1996). Insulin Regulation of Phosphoenolpyruvate Carboxykinase Gene Expression Does Not Require Activation of the Ras/Mitogen-activated Protein Kinase Signaling Pathway. J. Biol. Chem. 271: 1890-1897 [Abstract] [Full Text]  
  • Haruta, T., Morris, A. J., Rose, D. W., Nelson, J. G., Mueckler, M., Olefsky, J. M. (1995). Insulin-stimulated GLUT4 Translocation Is Mediated by a Divergent Intracellular Signaling Pathway. J. Biol. Chem. 270: 27991-27994 [Abstract] [Full Text]  
  • Yao, R, Cooper, G. (1995). Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267: 2003-2006 [Abstract]  
  • Wiese, R. J., Mastick, C. C., Lazar, D. F., Saltiel, A. R. (1995). Activation of Mitogen-activated Protein Kinase and Phosphatidylinositol 3`-Kinase Is Not Sufficient for the Hormonal Stimulation of Glucose Uptake, Lipogenesis, or Glycogen Synthesis in 3T3-L1 Adipocytes. J. Biol. Chem. 270: 3442-3446 [Abstract] [Full Text]  
  • Kong, M., Mounier, C., Wu, J., Posner, B. I. (2000). Epidermal Growth Factor-induced Phosphatidylinositol 3-Kinase Activation and DNA Synthesis. IDENTIFICATION OF Grb2-ASSOCIATED BINDER 2 AS THE MAJOR MEDIATOR IN RAT HEPATOCYTES. J. Biol. Chem. 275: 36035-36042 [Abstract] [Full Text]  
  • Goalstone, M. L., Leitner, J. W., Berhanu, P., Sharma, P. M., Olefsky, J. M., Draznin, B. (2001). Insulin Signals to Prenyltransferases via the Shc Branch of Intracellular Signaling. J. Biol. Chem. 276: 12805-12812 [Abstract] [Full Text]  
  • Yoo, M.-H., Woo, C.-H., You, H.-J., Cho, S.-H., Kim, B.-C., Choi, J.-E., Chun, J.-S., Jhun, B. H., Kim, T.-S., Kim, J.-H. (2001). Role of the Cytosolic Phospholipase A2-linked Cascade in Signaling by an Oncogenic, Constitutively Active Ha-Ras Isoform. J. Biol. Chem. 276: 24645-24653 [Abstract] [Full Text]  
  • Gineitis, D., Treisman, R. (2001). Differential Usage of Signal Transduction Pathways Defines Two Types of Serum Response Factor Target Gene. J. Biol. Chem. 276: 24531-24539 [Abstract] [Full Text]  
  • Geddis, A. E., Fox, N. E., Kaushansky, K. (2001). Phosphatidylinositol 3-Kinase Is Necessary but Not Sufficient for Thrombopoietin-induced Proliferation in Engineered Mpl-bearing Cell Lines as Well as in Primary Megakaryocytic Progenitors. J. Biol. Chem. 276: 34473-34479 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»