Dissection of the insulin signaling pathway via quantitative phosphoproteomics (2008)
Krüger, M., Kratchmarova, I., Blagoev, B., Tseng, Y. H., Kahn, C. R., Mann, M.
Role for neuronal insulin resistance in neurodegenerative diseases (2004)
Schubert, M., Gautam, D., Surjo, D., Ueki, Kazuhiro, Baudler, S., Schubert, D., ...
Role for neuronal insulin resistance in neurodegenerative diseases (2004)
Schubert, M., Gautam, D., Surjo, D., Ueki, Kazuhiro, Baudler, S., Schubert, D., ...
Cross-talk between the insulin and angiotensin signaling systems.
Velloso, L A, Folli, F, Sun, X J, White, M F, Saad, M J, Kahn, C R
Angiotensin II (AII), acting via its G-protein linked receptor, is an important regulator of cardiac, vascular, and renal function. Following injection of AII into rats, we find that there is also a...
Rothman, D L, Magnusson, I, Cline, G, Gerard, D, Kahn, C R, Shulman, R G, ...
Recent studies have demonstrated that reduced insulin-stimulated muscle glycogen synthesis is the major cause of insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM)....
Chuang, L M, Myers, M G, Seidner, G A, Birnbaum, M J, White, M F, Kahn, C R
Insulin and insulin-like growth factor I (IGF-I) initiate cellular functions by activating their homologous tyrosine kinase receptors. In most mammalian cell types, this results in rapid tyrosine...
Goncalves, E, Yamada, K, Thatte, H S, Backer, J M, Golan, D E, Kahn, C R, ...
Transmembrane (TM) domains of integral membrane proteins are generally thought to be helical. However, a Gly-Pro sequence within the TM domain of the insulin receptor is predicted to act as a helix...
Cheatham, B, Shoelson, S E, Yamada, K, Goncalves, E, Kahn, C R
The mechanism through which insulin binding to the extracellular domain of the insulin receptor activates the intrinsic tyrosine kinase in the intracellular domain of the protein is unknown. For the...
Wilden, P A, Backer, J M, Kahn, C R, Cahill, D A, Schroeder, G J, White, M F
We have studied the function of a mutant insulin receptor (IR) molecule in which Tyr-1146, one of the first autophosphorylation sites in the beta subunit, was replaced with phenylalanine (IRF1146)....
Antonetti, D A, Algenstaedt, P, Kahn, C R
We have identified two novel alternatively spliced forms of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase by expression screening of a human skeletal muscle library with...
Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1-deficient cells.
Brüning, J C, Winnay, J, Cheatham, B, Kahn, C R
Mice made insulin receptor substrate 1 (IRS-1) deficient by targeted gene knockout exhibit growth retardation and abnormal glucose metabolism due to resistance to the actions of insulin-like growth...
Backer, J M, Kahn, C R, White, M F
The relation between insulin-stimulated autophosphorylation of the insulin receptor and internalization of the receptor was studied in Fao rat hepatoma cells. Treatment of Fao cells with...
Gross, D J, Halban, P A, Kahn, C R, Weir, G C, Villa-Komaroff, L
A patient with type II diabetes associated with hyperproinsulinemia has been shown to have a point mutation in one insulin gene allele, resulting in replacement of histidine with aspartic acid at...
Folli, F, Saad, M J, Backer, J M, Kahn, C R
Insulin stimulates tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), which in turn binds to and activates phosphatidylinositol 3-kinase (PI 3-kinase). In the present study, we have...
Saad, M J, Folli, F, Kahn, J A, Kahn, C R
Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1), which in turn associates with...
Vanadate normalizes hyperglycemia in two mouse models of non-insulin-dependent diabetes mellitus.
Meyerovitch, J, Rothenberg, P, Shechter, Y, Bonner-Weir, S, Kahn, C R
We have studied the effects of oral administration of vanadate, an insulinometic agent and a potent inhibitor of phosphotyrosyl protein phosphatase (PTPase) in vitro, on blood glucose and PTPase...
Pedersen, O, Kahn, C R, Kahn, B B
We have studied the relationship between glucose uptake rate and Glut 1 and Glut 4 protein and mRNA levels per fat cell in lean (FA/FA) and obese (fa/fa) Zucker rats at 5, 10, and 20 wk of age, and...
Kwok, C F, Goldstein, B J, Muller-Wieland, D, Lee, T S, Kahn, C R, King, G L
Insulin actions and receptors were studied in capillary endothelial cells cultured from diabetic BB rats and their nondiabetic colony mates. The endothelial cells from diabetic rats of 2 mo duration...
Leprechaunism is a rare genetic disorder characterized by severe growth retardation and insulin resistance. Maximal epidermal growth factor (EGF) binding was reduced in fibroblasts from three...
Hedo, J A, Kasuga, M, Van Obberghen, E, Roth, J, Kahn, C R
Insulin receptors of human lymphocytes (IM-9 line) were biosynthetically labeled with [3H]glucosamine, [3H]galactose, [3H]fucose, or [3H]mannose. After solubilization in Triton X-100, cell extracts...
Hepatic phosphotyrosine phosphatase activity and its alterations in diabetic rats.
Meyerovitch, J, Backer, J M, Kahn, C R
Phosphotyrosine phosphatase (PTPase) activity in rat liver was measured using a phosphopeptide substrate containing sequence identity to the major site of insulin receptor autophosphorylation. PTPase...
Four RFLPs of the human insulin receptor gene: PstI, KpnI, RsaI (2 RFLPs).
Cox, N J, Spielman, R S, Kahn, C R, Muller-Wieland, D, Kriauciunas, K M, Taub, R
Bar, R S, Gorden, P, Roth, J, Kahn, C R, De Meyts, P
The binding of 125I-insulin to insulin receptors on circulating monocytes of obese patients and normal volunteers has been determined under various dietary states. In the basal, fed state the...
Flier, J S, Kahn, C R, Jarrett, D B, Roth, J
We have characterized the circulating inhibitor of insulin receptor binding found in several patients with a new syndrome of extreme insulin resistance. The inhibitor is an immunoglobulin by multiple...
Four RFLPs of the human insulin receptor gene: PstI, KpnI, RsaI (2 RFLPs).
Cox, N J, Spielman, R S, Kahn, C R, Müller-Wieland, D, Kriauciunas, K M, Taub, R
Kasuga, M, Kahn, C R, Hedo, J A, Van Obberghen, E, Yamada, K M
We have measured the turnover rate of the polypeptide subunits of the insulin receptor in cultured human lymphocytes (IM-9 line) and have investigated the mechanism of insulin-induced receptor loss....
Cheatham, B, Vlahos, C J, Cheatham, L, Wang, L, Blenis, J, Kahn, C R
Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by insulin and a variety of growth factors, but its exact role in signal transduction remains unclear. We have used a novel, highly specific...
Chuang, L M, Myers, M G, Backer, J M, Shoelson, S E, White, M F, Birnbaum, M J, ...
Xenopus oocytes from unprimed frogs possess insulin-like growth factor I (IGF-I) receptors but lack insulin and IGF-I receptor substrate 1 (IRS-1), the endogenous substrate of this kinase, and fail...
Antireceptor antibodies as probes of insulinlike growth factor receptor structure.
Kasuga, M, Sasaki, N, Kahn, C R, Nissley, S P, Rechler, M M
Insulin receptors and Type I insulinlike growth factor (IGF) receptors have a similar structure with a major binding subunit of Mr approximately 130,000 linked by disulfide bonds to other membrane...
Virus-induced decrease of insulin receptors in cultured human cells.
Shimizu, F, Hooks, J J, Kahn, C R, Notkins, A L
Viral infections may produce abnormalities in carbohydrate metabolism in normal subjects and profound changes in glucose homeostasis in insulin-dependent diabetics. Using an in vitro radio-receptor...
Carpentier, J L, Gorden, P, Amherdt, M, Van Obberghen, E, Kahn, C R, Orci, L
Morphologic and biochemical studies indicate that the initial action of insulin is binding to a cell surface receptor. Whether further translocation of the hormone, or a product of the hormone,...
Analysis of the insulin receptor by anti-receptor antibodies and flow cytometry.
Maron, R, Jackson, R A, Jacobs, S, Eisenbarth, G, Kahn, C R
We characterized insulin receptors on a human lymphoblastoid cell line (IM-9) and studied their regulation using anti-receptor antibodies and fluorescence flow cytometry. The fluorescence intensity...
Takayama, S, White, M F, Lauris, V, Kahn, C R
The effect of the tumor-promoting agent phorbol 12-myristate 13-acetate (PMA) on insulin receptors and insulin action was studied in rat hepatoma cells in culture. PMA (0.1-1.0 micrograms/ml) did not...
King, G L, Kahn, C R, Heldin, C H
Insulins from the hystricomorphs (guinea pig, porcupine, coypu, and casiragua) at high concentration stimulate DNA synthesis in human fibroblasts to a greater level than other mammalian insulins or...
Tyrosine-specific protein kinase activity is associated with the purified insulin receptor.
Kasuga, M, Fujita-Yamaguchi, Y, Blithe, D L, Kahn, C R
Highly purified human placental insulin receptors were obtained by sequential affinity chromatography on wheat germ agglutinin and insulin-agarose. The preparation had an insulin binding capacity of...
King, G L, Goodman, A D, Buzney, S, Moses, A, Kahn, C R
It has been suggested that elevated levels of insulin or insulin-like growth factors (IGFs) play a role in the development of diabetic vascular complications. Previously, we have shown a differential...
Ammonium inhibits processing and cytotoxicity of reovirus, a nonenveloped virus.
Maratos-Flier, E, Goodman, M J, Murray, A H, Kahn, C R
Successful viral infection involves a series of interactions between the virus and the host cell. The outcome of viral infection is, in fact, dependent on intact cellular function; it is required for...
Sodoyez, J C, Sodoyez Goffaux, F, Von Frenckell, R, De Vos, C J, Treves, S, Kahn, C R
Anesthetized rats were treated with saline, antiinsulin receptor serum, or antiinsulin serum, and the biodistribution of high pressure liquid chromatography-purified 123I-Tyr A14-insulin was studied...
Jarrett, D B, Roth, J, Kahn, C R, Flier, J S
Autoantibodies directed against the cell surface receptors for insulin are found in some patients with extreme insulin resistance. These antibodies specifically inhibit the binding of insulin to its...
Schwartz, R H, Bianco, A R, Handwerger, B S, Kahn, C R
Insulin receptors have been demonstrated on mononuclear leukocytes prepared by centrifugation of buffy coats from normal blood donors on Ficoll-Hypaque gradients. The cell type that specifically...
Nonsuppressible insulin-like activity of human serum. A potent inhibitor of insulin degradation.
Kahn, C R, Megyesi, K, Roth, J
Nonsuppressible insulin-like activity soluble in acid ethanol (NSILA-s) is a well-characterized peptide derived from human serum which has previously been shown to have insulin-like bioactivity and...
King, G L, Buzney, S M, Kahn, C R, Hetu, N, Buchwald, S, Macdonald, S G, ...
The pathologies of diabetic micro- and macroangiopathy are different, suggesting that diabetes affects these two types of vascular tissue in a dissimilar manner. We have compared insulin receptors...
Antonetti, D A, Reynet, C, Kahn, C R
Screening subtraction libraries from normal and type II diabetic human skeletal muscle, we identified four different mitochondrially encoded genes which were increased in expression in diabetes. The...
Reddy, S S, Lauris, V, Kahn, C R
Insulin receptor function was examined in cultured skin fibroblasts from three patients with leprechaunism (Ark-1, Minn-1, and Can-1), a rare syndrome of severe insulin resistance and neonatal growth...
Saad, M J, Araki, E, Miralpeix, M, Rothenberg, P L, White, M F, Kahn, C R
Insulin rapidly stimulates tyrosine phosphorylation of a protein of approximately 185 kD in most cell types. This protein, termed insulin receptor substrate-1 (IRS-1), has been implicated in insulin...
Almind, K, Inoue, G, Pedersen, O, Kahn, C R
Insulin receptor substrates-1 (IRS-1) is the major cytoplasmic substrate of the insulin and IGF-1 receptors. Recent studies have identified multiple sequence variants of IRS-1, especially in patients...
Folli, F, Kahn, C R, Hansen, H, Bouchie, J L, Feener, E P
To investigate potential interactions between angiotensin II (AII) and the insulin signaling system in the vasculature, insulin and AII regulation of insulin receptor substrate-1 (IRS-1)...
Kerouz, N J, Hörsch, D, Pons, S, Kahn, C R
Intracellular insulin signaling involves a series of alternative and complementary pathways created by the multiple substrates of the insulin receptor (IRS) and the various isoforms of SH2 domain...
Bidirectional modulation of insulin action by amino acids.
Patti, M E, Brambilla, E, Luzi, L, Landaker, E J, Kahn, C R
Amino acids have been shown to stimulate protein synthesis, inhibit proteolysis, and decrease whole-body and forearm glucose disposal. Using cultured hepatoma and myotube cells, we demonstrate that...
Specific plasma membrane receptors for reovirus on rat pituitary cells in culture.
Maratos-Flier, E, Kahn, C R, Spriggs, D R, Fields, B N
Specific cellular and host tropism is a characteristic property of many viruses mediated by the interaction of viral attachment proteins with components of the plasma membrane of the cell. We have...
Mann, D L, Mendell, N, Kahn, C R, Johnson, A H, Rosenthal, A
Genes in the major histocompatibility complex of mice and guinea pigs control immunologic responsiveness to insulins from other animal species. In order to determine if similar genetic control exists...
Alarcón, C, Cheatham, B, Lincoln, B, Kahn, C R, Siddle, K, Rhodes, C J
The insulin proreceptor is cleaved by limited proteolysis post-translationally at an Arg-Lys-Arg-Arg site to generate its mature alpha- and beta-subunit form. An 35S-labelled insulin proreceptor...
Expression of insulin receptors and insulin action in cell hybrids and cybrids.
Kahn, C R, Lauris, V, Fehlmann, M, Crettaz, M
The expression of insulin receptors and insulin action was studied in cell hybrids and cybrids produced by fusion of the BWIJ mouse hepatoma cell line with nucleated and enucleated mouse L-cells...
Glucagon resistance of hepatoma cells. Evidence for receptor and post-receptor defects.
Fehlmann, M, Crettaz, M, Kahn, C R
Of all available liver cells in culture, only primary cultured hepatocytes are known to respond to glucagon in vitro. In the present study we investigated whether glucagon could stimulate amino acid...
After insulin receptor activation, many cytoplasmic enzymes, including mitogen-activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II (CKII) are activated, but exactly how...
Effects of phosphorylation on function of the Rad GTPase.
Moyers, J S, Zhu, J, Kahn, C R
Rad, Gem and Kir possess unique structural features in comparison with other Ras-like GTPases, including a C-terminal 31-residue extension that lacks typical prenylation motifs. We have recently...
Cross-talk between the insulin and angiotensin signaling systems.
Velloso, L A, Folli, F, Sun, X J, White, M F, Saad, M J, Kahn, C R
Angiotensin II (AII), acting via its G-protein linked receptor, is an important regulator of cardiac, vascular, and renal function. Following injection of AII into rats, we find that there is also a...
Rothman, D L, Magnusson, I, Cline, G, Gerard, D, Kahn, C R, Shulman, R G, ...
Recent studies have demonstrated that reduced insulin-stimulated muscle glycogen synthesis is the major cause of insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM)....
Chuang, L M, Myers, M G, Seidner, G A, Birnbaum, M J, White, M F, Kahn, C R
Insulin and insulin-like growth factor I (IGF-I) initiate cellular functions by activating their homologous tyrosine kinase receptors. In most mammalian cell types, this results in rapid tyrosine...
Goncalves, E, Yamada, K, Thatte, H S, Backer, J M, Golan, D E, Kahn, C R, ...
Transmembrane (TM) domains of integral membrane proteins are generally thought to be helical. However, a Gly-Pro sequence within the TM domain of the insulin receptor is predicted to act as a helix...
Cheatham, B, Shoelson, S E, Yamada, K, Goncalves, E, Kahn, C R
The mechanism through which insulin binding to the extracellular domain of the insulin receptor activates the intrinsic tyrosine kinase in the intracellular domain of the protein is unknown. For the...
Wilden, P A, Backer, J M, Kahn, C R, Cahill, D A, Schroeder, G J, White, M F
We have studied the function of a mutant insulin receptor (IR) molecule in which Tyr-1146, one of the first autophosphorylation sites in the beta subunit, was replaced with phenylalanine (IRF1146)....
Antonetti, D A, Algenstaedt, P, Kahn, C R
We have identified two novel alternatively spliced forms of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase by expression screening of a human skeletal muscle library with...
Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1-deficient cells.
Brüning, J C, Winnay, J, Cheatham, B, Kahn, C R
Mice made insulin receptor substrate 1 (IRS-1) deficient by targeted gene knockout exhibit growth retardation and abnormal glucose metabolism due to resistance to the actions of insulin-like growth...
Backer, J M, Kahn, C R, White, M F
The relation between insulin-stimulated autophosphorylation of the insulin receptor and internalization of the receptor was studied in Fao rat hepatoma cells. Treatment of Fao cells with...
Gross, D J, Halban, P A, Kahn, C R, Weir, G C, Villa-Komaroff, L
A patient with type II diabetes associated with hyperproinsulinemia has been shown to have a point mutation in one insulin gene allele, resulting in replacement of histidine with aspartic acid at...
Folli, F, Saad, M J, Backer, J M, Kahn, C R
Insulin stimulates tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), which in turn binds to and activates phosphatidylinositol 3-kinase (PI 3-kinase). In the present study, we have...
Saad, M J, Folli, F, Kahn, J A, Kahn, C R
Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1), which in turn associates with...
Vanadate normalizes hyperglycemia in two mouse models of non-insulin-dependent diabetes mellitus.
Meyerovitch, J, Rothenberg, P, Shechter, Y, Bonner-Weir, S, Kahn, C R
We have studied the effects of oral administration of vanadate, an insulinometic agent and a potent inhibitor of phosphotyrosyl protein phosphatase (PTPase) in vitro, on blood glucose and PTPase...
Pedersen, O, Kahn, C R, Kahn, B B
We have studied the relationship between glucose uptake rate and Glut 1 and Glut 4 protein and mRNA levels per fat cell in lean (FA/FA) and obese (fa/fa) Zucker rats at 5, 10, and 20 wk of age, and...
Kwok, C F, Goldstein, B J, Muller-Wieland, D, Lee, T S, Kahn, C R, King, G L
Insulin actions and receptors were studied in capillary endothelial cells cultured from diabetic BB rats and their nondiabetic colony mates. The endothelial cells from diabetic rats of 2 mo duration...
Leprechaunism is a rare genetic disorder characterized by severe growth retardation and insulin resistance. Maximal epidermal growth factor (EGF) binding was reduced in fibroblasts from three...
Hedo, J A, Kasuga, M, Van Obberghen, E, Roth, J, Kahn, C R
Insulin receptors of human lymphocytes (IM-9 line) were biosynthetically labeled with [3H]glucosamine, [3H]galactose, [3H]fucose, or [3H]mannose. After solubilization in Triton X-100, cell extracts...
Hepatic phosphotyrosine phosphatase activity and its alterations in diabetic rats.
Meyerovitch, J, Backer, J M, Kahn, C R
Phosphotyrosine phosphatase (PTPase) activity in rat liver was measured using a phosphopeptide substrate containing sequence identity to the major site of insulin receptor autophosphorylation. PTPase...
Four RFLPs of the human insulin receptor gene: PstI, KpnI, RsaI (2 RFLPs).
Cox, N J, Spielman, R S, Kahn, C R, Muller-Wieland, D, Kriauciunas, K M, Taub, R
Bar, R S, Gorden, P, Roth, J, Kahn, C R, De Meyts, P
The binding of 125I-insulin to insulin receptors on circulating monocytes of obese patients and normal volunteers has been determined under various dietary states. In the basal, fed state the...
Flier, J S, Kahn, C R, Jarrett, D B, Roth, J
We have characterized the circulating inhibitor of insulin receptor binding found in several patients with a new syndrome of extreme insulin resistance. The inhibitor is an immunoglobulin by multiple...
Four RFLPs of the human insulin receptor gene: PstI, KpnI, RsaI (2 RFLPs).
Cox, N J, Spielman, R S, Kahn, C R, Müller-Wieland, D, Kriauciunas, K M, Taub, R
Kasuga, M, Kahn, C R, Hedo, J A, Van Obberghen, E, Yamada, K M
We have measured the turnover rate of the polypeptide subunits of the insulin receptor in cultured human lymphocytes (IM-9 line) and have investigated the mechanism of insulin-induced receptor loss....
Cheatham, B, Vlahos, C J, Cheatham, L, Wang, L, Blenis, J, Kahn, C R
Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by insulin and a variety of growth factors, but its exact role in signal transduction remains unclear. We have used a novel, highly specific...
Chuang, L M, Myers, M G, Backer, J M, Shoelson, S E, White, M F, Birnbaum, M J, ...
Xenopus oocytes from unprimed frogs possess insulin-like growth factor I (IGF-I) receptors but lack insulin and IGF-I receptor substrate 1 (IRS-1), the endogenous substrate of this kinase, and fail...
Antireceptor antibodies as probes of insulinlike growth factor receptor structure.
Kasuga, M, Sasaki, N, Kahn, C R, Nissley, S P, Rechler, M M
Insulin receptors and Type I insulinlike growth factor (IGF) receptors have a similar structure with a major binding subunit of Mr approximately 130,000 linked by disulfide bonds to other membrane...
Virus-induced decrease of insulin receptors in cultured human cells.
Shimizu, F, Hooks, J J, Kahn, C R, Notkins, A L
Viral infections may produce abnormalities in carbohydrate metabolism in normal subjects and profound changes in glucose homeostasis in insulin-dependent diabetics. Using an in vitro radio-receptor...
Carpentier, J L, Gorden, P, Amherdt, M, Van Obberghen, E, Kahn, C R, Orci, L
Morphologic and biochemical studies indicate that the initial action of insulin is binding to a cell surface receptor. Whether further translocation of the hormone, or a product of the hormone,...
Analysis of the insulin receptor by anti-receptor antibodies and flow cytometry.
Maron, R, Jackson, R A, Jacobs, S, Eisenbarth, G, Kahn, C R
We characterized insulin receptors on a human lymphoblastoid cell line (IM-9) and studied their regulation using anti-receptor antibodies and fluorescence flow cytometry. The fluorescence intensity...
Takayama, S, White, M F, Lauris, V, Kahn, C R
The effect of the tumor-promoting agent phorbol 12-myristate 13-acetate (PMA) on insulin receptors and insulin action was studied in rat hepatoma cells in culture. PMA (0.1-1.0 micrograms/ml) did not...
King, G L, Kahn, C R, Heldin, C H
Insulins from the hystricomorphs (guinea pig, porcupine, coypu, and casiragua) at high concentration stimulate DNA synthesis in human fibroblasts to a greater level than other mammalian insulins or...
Tyrosine-specific protein kinase activity is associated with the purified insulin receptor.
Kasuga, M, Fujita-Yamaguchi, Y, Blithe, D L, Kahn, C R
Highly purified human placental insulin receptors were obtained by sequential affinity chromatography on wheat germ agglutinin and insulin-agarose. The preparation had an insulin binding capacity of...
King, G L, Goodman, A D, Buzney, S, Moses, A, Kahn, C R
It has been suggested that elevated levels of insulin or insulin-like growth factors (IGFs) play a role in the development of diabetic vascular complications. Previously, we have shown a differential...
Ammonium inhibits processing and cytotoxicity of reovirus, a nonenveloped virus.
Maratos-Flier, E, Goodman, M J, Murray, A H, Kahn, C R
Successful viral infection involves a series of interactions between the virus and the host cell. The outcome of viral infection is, in fact, dependent on intact cellular function; it is required for...
Sodoyez, J C, Sodoyez Goffaux, F, Von Frenckell, R, De Vos, C J, Treves, S, Kahn, C R
Anesthetized rats were treated with saline, antiinsulin receptor serum, or antiinsulin serum, and the biodistribution of high pressure liquid chromatography-purified 123I-Tyr A14-insulin was studied...
Jarrett, D B, Roth, J, Kahn, C R, Flier, J S
Autoantibodies directed against the cell surface receptors for insulin are found in some patients with extreme insulin resistance. These antibodies specifically inhibit the binding of insulin to its...
Schwartz, R H, Bianco, A R, Handwerger, B S, Kahn, C R
Insulin receptors have been demonstrated on mononuclear leukocytes prepared by centrifugation of buffy coats from normal blood donors on Ficoll-Hypaque gradients. The cell type that specifically...
Nonsuppressible insulin-like activity of human serum. A potent inhibitor of insulin degradation.
Kahn, C R, Megyesi, K, Roth, J
Nonsuppressible insulin-like activity soluble in acid ethanol (NSILA-s) is a well-characterized peptide derived from human serum which has previously been shown to have insulin-like bioactivity and...
King, G L, Buzney, S M, Kahn, C R, Hetu, N, Buchwald, S, Macdonald, S G, ...
The pathologies of diabetic micro- and macroangiopathy are different, suggesting that diabetes affects these two types of vascular tissue in a dissimilar manner. We have compared insulin receptors...
Antonetti, D A, Reynet, C, Kahn, C R
Screening subtraction libraries from normal and type II diabetic human skeletal muscle, we identified four different mitochondrially encoded genes which were increased in expression in diabetes. The...
Reddy, S S, Lauris, V, Kahn, C R
Insulin receptor function was examined in cultured skin fibroblasts from three patients with leprechaunism (Ark-1, Minn-1, and Can-1), a rare syndrome of severe insulin resistance and neonatal growth...
Saad, M J, Araki, E, Miralpeix, M, Rothenberg, P L, White, M F, Kahn, C R
Insulin rapidly stimulates tyrosine phosphorylation of a protein of approximately 185 kD in most cell types. This protein, termed insulin receptor substrate-1 (IRS-1), has been implicated in insulin...
Almind, K, Inoue, G, Pedersen, O, Kahn, C R
Insulin receptor substrates-1 (IRS-1) is the major cytoplasmic substrate of the insulin and IGF-1 receptors. Recent studies have identified multiple sequence variants of IRS-1, especially in patients...
Folli, F, Kahn, C R, Hansen, H, Bouchie, J L, Feener, E P
To investigate potential interactions between angiotensin II (AII) and the insulin signaling system in the vasculature, insulin and AII regulation of insulin receptor substrate-1 (IRS-1)...
Kerouz, N J, Hörsch, D, Pons, S, Kahn, C R
Intracellular insulin signaling involves a series of alternative and complementary pathways created by the multiple substrates of the insulin receptor (IRS) and the various isoforms of SH2 domain...
Bidirectional modulation of insulin action by amino acids.
Patti, M E, Brambilla, E, Luzi, L, Landaker, E J, Kahn, C R
Amino acids have been shown to stimulate protein synthesis, inhibit proteolysis, and decrease whole-body and forearm glucose disposal. Using cultured hepatoma and myotube cells, we demonstrate that...
Specific plasma membrane receptors for reovirus on rat pituitary cells in culture.
Maratos-Flier, E, Kahn, C R, Spriggs, D R, Fields, B N
Specific cellular and host tropism is a characteristic property of many viruses mediated by the interaction of viral attachment proteins with components of the plasma membrane of the cell. We have...
Mann, D L, Mendell, N, Kahn, C R, Johnson, A H, Rosenthal, A
Genes in the major histocompatibility complex of mice and guinea pigs control immunologic responsiveness to insulins from other animal species. In order to determine if similar genetic control exists...
Alarcón, C, Cheatham, B, Lincoln, B, Kahn, C R, Siddle, K, Rhodes, C J
The insulin proreceptor is cleaved by limited proteolysis post-translationally at an Arg-Lys-Arg-Arg site to generate its mature alpha- and beta-subunit form. An 35S-labelled insulin proreceptor...
Expression of insulin receptors and insulin action in cell hybrids and cybrids.
Kahn, C R, Lauris, V, Fehlmann, M, Crettaz, M
The expression of insulin receptors and insulin action was studied in cell hybrids and cybrids produced by fusion of the BWIJ mouse hepatoma cell line with nucleated and enucleated mouse L-cells...
Glucagon resistance of hepatoma cells. Evidence for receptor and post-receptor defects.
Fehlmann, M, Crettaz, M, Kahn, C R
Of all available liver cells in culture, only primary cultured hepatocytes are known to respond to glucagon in vitro. In the present study we investigated whether glucagon could stimulate amino acid...
After insulin receptor activation, many cytoplasmic enzymes, including mitogen-activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II (CKII) are activated, but exactly how...
Effects of phosphorylation on function of the Rad GTPase.
Moyers, J S, Zhu, J, Kahn, C R
Rad, Gem and Kir possess unique structural features in comparison with other Ras-like GTPases, including a C-terminal 31-residue extension that lacks typical prenylation motifs. We have recently...