Lipid phosphatases as drug discovery targets for type 2 diabetes (original) (raw)
Amos, A. F., McCarty, D. J. & Zimmet, P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet. Med.14 (Suppl. 5), S1–S85 (1997). PubMed Google Scholar
Pessin, J. E. & Saltiel, A. R. Signaling pathways in insulin action: molecular targets of insulin resistance. J. Clin. Invest.106, 165–169 (2000). ArticleCASPubMedPubMed Central Google Scholar
Saltiel, A. R. & Kahn, C. R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature414, 799–806 (2001). ArticleCASPubMed Google Scholar
Patti, M. E. & Kahn, C. R. The insulin receptor-a critical link in glucose homeostasis and insulin action. J. Basic Clin. Physiol. Pharmacol.9, 89–109 (1998). ArticleCASPubMed Google Scholar
White, M. F. The IRS-signalling system: a network of docking proteins that mediate insulin action. Mol. Cell. Biochem.182, 3–11 (1998). ArticleCASPubMed Google Scholar
Sun, X. J. et al. Role of IRS-2 in insulin and cytokine signalling. Nature377, 173–177 (1995). ArticleCASPubMed Google Scholar
Lavan, B. E. et al. A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family. J. Biol. Chem.272, 21403–21407 (1997). ArticleCASPubMed Google Scholar
Lavan, B. E., Lane, W. S. & Lienhard, G. E. The 60-kDa phosphotyrosine protein in insulin-treated adipocytes is a new member of the insulin receptor substrate family. J. Biol. Chem.272, 11439–11443 (1997). ArticleCASPubMed Google Scholar
Sasaoka, T. et al. Evidence for a functional role of Shc proteins in mitogenic signaling induced by insulin, insulin-like growth factor-1, and epidermal growth factor. J. Biol. Chem.269, 13689–13694 (1994). ArticleCASPubMed Google Scholar
Liu, J., Kimura, A., Baumann, C. A. & Saltiel, A. R. APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. Mol. Cell. Biol.22, 3599–3609 (2002). ArticleCASPubMedPubMed Central Google Scholar
Ribon, V. & Saltiel, A. R. Insulin stimulates tyrosine phos-phorylation of the proto-oncogene product of c-Cbl in 3T3-L1 adipocytes. Biochem. J.324, 839–845 (1997). ArticleCASPubMedPubMed Central Google Scholar
Holgado-Madruga, M., Emlet, D. R., Moscatello, D. K., Godwin, A. K. & Wong, A. J. A Grb2-associated docking protein in EGF- and insulin-receptor signalling. Nature379, 560–564 (1996). ArticleCASPubMed Google Scholar
Withers, D. J. et al. Disruption of IRS-2 causes type 2 diabetes in mice. Nature391, 900–904 (1998). ArticleCASPubMed Google Scholar
Tamemoto, H. et al. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature372, 182–186 (1994). ArticleCASPubMed Google Scholar
Araki, E. et al. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature372, 186–190 (1994). ArticleCASPubMed Google Scholar
Bruning, J. C. et al. Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell88, 561–572 (1997). ArticleCASPubMed Google Scholar
Kido, Y., Nakae, J. & Accili, D. Clinical review 125: The insulin receptor and its cellular targets. J. Clin. Endocrinol. Metab.86, 972–979 (2001). CASPubMed Google Scholar
Okada, T., Kawano, Y., Sakakibara, T., Hazeki, O. & Ui, M. Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. J. Biol. Chem.269, 3568–3573 (1994). One of the earliest studies to suggest a crucial role for insulin-stimulated PI3K activity in producing the metabolic responses to the hormone. Subsequent investigations have corroborated and expanded on these initial observations, leading to the recognition that PI3K activation has a major role in most metabolic responses to insulin. ArticleCASPubMed Google Scholar
Cheatham, B. et al. Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol.14, 4902–4911 (1994). While providing independent evidence for a connection between insulin-stimulated PI3K activity and metabolic responses, divergence in insulin signalling was proposed whereby PI3K does not significantly affect MAPK phosphorylation. Such data supports the existence of divergent pathways promoting the metabolic versus mitogenic responses to insulin. CASPubMedPubMed Central Google Scholar
Evans, J. L., Honer, C. M., Womelsdorf, B. E., Kaplan, E. L. & Bell, P. A. The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis. Cell Signal.7, 365–376 (1995). ArticleCASPubMed Google Scholar
Quon, M. J. et al. Roles of 1-phosphatidylinositol 3-kinase and ras in regulating translocation of GLUT4 in transfected rat adipose cells. Mol. Cell. Biol.15, 5403–5411 (1995). ArticleCASPubMedPubMed Central Google Scholar
Martin, S. S. et al. Activated phosphatidylinositol 3-kinase is sufficient to mediate actin rearrangement and GLUT4 translocation in 3T3-L1 adipocytes. J. Biol. Chem.271, 17605–17608 (1996). ArticleCASPubMed Google Scholar
Mora, A., Komander, D., van Aalten, D. M. & Alessi, D. R. PDK1, the master regulator of AGC kinase signal transduction. Semin. Cell Dev. Biol.15, 161–170 (2004). ArticleCASPubMed Google Scholar
Sarbassov, D. D., Guertin, D. A., Ali, S. M. & Sabatini, D. M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science307, 1098–1101 (2005). ArticleCASPubMed Google Scholar
Niswender, K. D. et al. Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. Diabetes52, 227–231 (2003). ArticleCASPubMed Google Scholar
Carvalheira, J. B. et al. Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats. Diabetologia46, 1629–1640 (2003). ArticleCASPubMed Google Scholar
Niswender, K. D. et al. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature413, 794–795 (2001). ArticleCASPubMed Google Scholar
Zhao, A. Z., Huan, J. N., Gupta, S., Pal, R. & Sahu, A. A phosphatidylinositol 3-kinase phosphodiesterase 3B-cyclic AMP pathway in hypothalamic action of leptin on feeding. Nature Neurosci.5, 727–728 (2002). ArticleCASPubMed Google Scholar
Rahmouni, K., Haynes, W. G., Morgan, D. A. & Mark, A. L. Intracellular mechanisms involved in leptin regulation of sympathetic outflow. Hypertension41, 763–767 (2003). ArticleCASPubMed Google Scholar
Goberdhan, D. C. & Wilson, C. PTEN: tumour suppressor, multifunctional growth regulator and more. Hum. Mol. Genet.12, R239–R248 (2003). ArticleCASPubMed Google Scholar
Leslie, N. R. & Downes, C. P. PTEN function: how normal cells control it and tumour cells lose it. Biochem. J.382, 1–11 (2004). Review of PTEN biology, including its role in signal transduction and mechanisms believed to modulate PTEN activity level. Discussion of the compelling evidence for PTEN as an important tumour suppressor powerfully conveys the significance of this issue to any PTEN inhibitor drug discovery effort. ArticleCASPubMedPubMed Central Google Scholar
Ogg, S. & Ruvkun, G. The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol. Cell2, 887–893 (1998). Important observation that precipitated numerous investigations exploring the capacity of this lipid phosphatase (PTEN) to regulatein vivoinsulin signalling. ArticleCASPubMed Google Scholar
Goberdhan, D. C., Paricio, N., Goodman, E. C., Mlodzik, M. & Wilson, C. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev.13, 3244–3258 (1999). ArticleCASPubMedPubMed Central Google Scholar
Nakashima, N., Sharma, P. M., Imamura, T., Bookstein, R. & Olefsky, J. M. The tumor suppressor PTEN negatively regulates insulin signaling in 3T3-L1 adipocytes. J. Biol. Chem.275, 12889–12895 (2000). ArticleCASPubMed Google Scholar
Ono, H. et al. 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 (2001). ArticleCASPubMed Google Scholar
Mosser, V. A., Li, Y. & Quon, M. J. PTEN does not modulate GLUT4 translocation in rat adipose cells under physiological conditions. Biochem. Biophys. Res. Commun.288, 1011–1017 (2001). ArticleCASPubMed Google Scholar
Tang, X., Powelka, A. M., Soriano, N. A., Czech, M. P. & Guilherme, A. PTEN, but not SHIP2, suppresses insulin signaling through the phosphatidylinositol 3-kinase/Akt pathway in 3T3-L1 adipocytes. J. Biol. Chem.280, 22523–22529 (2005). ArticleCASPubMed Google Scholar
Seo, J. H., Ahn, Y., Lee, S. R., Yeol Yeo, C. & Chung Hur, K. The major target of the endogenously generated reactive oxygen species in response to insulin stimulation is phosphatase and tensin homolog and not phosphoinositide-3 kinase (PI-3 kinase) in the PI-3 kinase/Akt pathway. Mol. Biol. Cell16, 348–357 (2005). ArticleCASPubMedPubMed Central Google Scholar
Butler, M. et al. Specific inhibition of PTEN expression reverses hyperglycemia in diabetic mice. Diabetes51, 1028–1034 (2002). First evidence thatin vivosuppression of PTEN expression might enhance insulin signalling and provide efficacy against type 2 diabetes. ArticleCASPubMed Google Scholar
Horie, Y. et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J. Clin. Invest.113, 1774–1783 (2004). Dramatic evidence that severe adverse effects of PTEN inhibition in the liver would likely limit the usefulness of any PTEN inhibitor hitting that important insulin-sensitive tissue. ArticleCASPubMedPubMed Central Google Scholar
Stiles, B. et al. Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. Proc. Natl Acad. Sci. USA101, 2082–2087 (2004). ArticleCASPubMedPubMed Central Google Scholar
Wijesekara, N. et al. Muscle-specific Pten deletion protects against insulin resistance and diabetes. Mol. Cell. Biol.25, 1135–1145 (2005). ArticleCASPubMedPubMed Central Google Scholar
Kurlawalla-Martinez, C. et al. Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. Mol. Cell. Biol.25, 2498–2510 (2005). ArticleCASPubMedPubMed Central Google Scholar
Lo, Y. T., Tsao, C. J., Liu, I. M., Liou, S. S. & Cheng, J. T. Increase of PTEN gene expression in insulin resistance. Horm. Metab. Res.36, 662–666 (2004). ArticleCASPubMed Google Scholar
Hansen, L. et al. Studies of variability in the PTEN gene among Danish caucasian patients with Type II diabetes mellitus. Diabetologia44, 237–240 (2001). ArticleCASPubMed Google Scholar
Ishihara, H. et al. Association of the polymorphisms in the 5′-untranslated region of PTEN gene with type 2 diabetes in a Japanese population. FEBS Lett.554, 450–454 (2003). ArticleCASPubMed Google Scholar
Rohrschneider, L. R., Fuller, J. F., Wolf, I., Liu, Y. & Lucas, D. M. Structure, function, and biology of SHIP proteins. Genes Dev.14, 505–520 (2000). ArticleCASPubMed Google Scholar
Pesesse, X., Deleu, S., De Smedt, F., Drayer, L. & Erneux, C. Identification of a second SH2-domain-containing protein closely related to the phosphatidyl-inositol polyphosphate 5-phosphatase SHIP. Biochem. Biophys. Res. Commun.239, 697–700 (1997). ArticleCASPubMed Google Scholar
Backers, K., Blero, D., Paternotte, N., Zhang, J. & Erneux, C. The termination of PI3K signalling by SHIP1 and SHIP2 inositol 5-phosphatases. Adv. Enzyme Regul.43, 15–28 (2003). ArticleCASPubMed Google Scholar
Chi, Y. et al. Comparative mechanistic and substrate specificity study of inositol polyphosphate 5-phosphatase Schizosaccharomyces pombe Synaptojanin and SHIP2. J. Biol. Chem.279, 44987–44995 (2004). ArticleCASPubMed Google Scholar
Kalesnikoff, J. et al. The role of SHIP in cytokine-induced signaling. Rev. Physiol. Biochem. Pharmacol.149, 87–103 (2003). ArticleCASPubMed Google Scholar
Sleeman, M. W. et al. Absence of the lipid phosphatase SHIP2 confers resistance to dietary obesity. Nature Med.11, 199–205 (2005). Second report of the experimental deletion of theShip2gene in mice. Anti-obesity phenotype of theseShip2knockout mice has prompted significant discussion of peripheral and/or central mechanisms by which SHIP2 might have such a profound effect on energy metabolism. ArticleCASPubMed Google Scholar
Ishihara, H. et al. Membrane localization of Src homology 2-containing inositol 5′-phosphatase 2 via Shc association is required for the negative regulation of insulin signaling in Rat1 fibroblasts overexpressing insulin receptors. Mol. Endocrinol.16, 2371–2381 (2002). ArticleCASPubMed Google Scholar
Dyson, J. M. et al. The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2, binds filamin and regulates submembraneous actin. J. Cell. Biol.155, 1065–1079 (2001). ArticleCASPubMedPubMed Central Google Scholar
Damen, J. E., Ware, M. D., Kalesnikoff, J., Hughes, M. R. & Krystal, G. SHIP's C-terminus is essential for its hydrolysis of PIP3 and inhibition of mast cell degranulation. Blood97, 1343–1351 (2001). ArticleCASPubMed Google Scholar
Liu, L. et al. The Src homology 2 (SH2) domain of SH2-containing inositol phosphatase (SHIP) is essential for tyrosine phosphorylation of SHIP, its association with Shc, and its induction of apoptosis. J. Biol. Chem.272, 8983–8988 (1997). ArticleCASPubMed Google Scholar
Dyson, J. M. et al. The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2. Int. J. Biochem. Cell Biol.37, 2260–2265 (2005). ArticleCASPubMed Google Scholar
Habib, T., Hejna, J. A., Moses, R. E. & Decker, S. J. Growth factors and insulin stimulate tyrosine phosphorylation of the 51C/SHIP2 protein. J. Biol. Chem.273, 18605–18609 (1998). ArticleCASPubMed Google Scholar
Ishihara, H. et al. Molecular cloning of rat SH2-containing inositol phosphatase 2 (SHIP2) and its role in the regulation of insulin signaling. Biochem. Biophys. Res. Commun.260, 265–272 (1999). ArticleCASPubMed Google Scholar
Blero, D. et al. The SH2 domain containing inositol 5-phosphatase SHIP2 controls phosphatidylinositol 3,4,5-trisphosphate levels in CHO-IR cells stimulated by insulin. Biochem. Biophys. Res. Commun.282, 839–843 (2001). ArticleCASPubMed Google Scholar
Wada, T. et al. Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5′-phosphatase catalytic activity. Mol. Cell. Biol.21, 1633–1646 (2001). ArticleCASPubMedPubMed Central Google Scholar
Sasaoka, T. et al. SH2-containing inositol phosphatase 2 predominantly regulates Akt2, and not Akt1, phosphorylation at the plasma membrane in response to insulin in 3T3-L1 adipocytes. J. Biol. Chem.279, 14835–14843 (2004). ArticleCASPubMed Google Scholar
Wada, T. et al. 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. Endocrinology140, 4585–4594 (1999). ArticleCASPubMed Google Scholar
Sharma, P. M., Son, H. S., Ugi, S., Ricketts, W. & Olefsky, J. M. Mechanism of SHIP-mediated inhibition of insulin- and platelet-derived growth factor-stimulated mitogen-activated protein kinase activity in 3T3-L1 adipocytes. Mol. Endocrinol.19, 421–430 (2005). ArticleCASPubMed Google Scholar
Sasaoka, T. et al. SH2-containing inositol phosphatase 2 negatively regulates insulin-induced glycogen synthesis in L6 myotubes. Diabetologia44, 1258–1267 (2001). ArticleCASPubMed Google Scholar
Murakami, S. et al. Impact of Src homology 2-containing inositol 5′-phosphatase 2 on the regulation of insulin signaling leading to protein synthesis in 3T3-L1 adipocytes cultured with excess amino acids. Endocrinology145, 3215–3223 (2004). ArticleCASPubMed Google Scholar
Cho, H. et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ). Science292, 1728–1731 (2001). ArticleCASPubMed Google Scholar
Bae, S. S., Cho, H., Mu, J. & Birnbaum, M. J. Isoform-specific regulation of insulin-dependent glucose uptake by Akt/protein kinase B. J. Biol. Chem.278, 49530–49536 (2003). ArticleCASPubMed Google Scholar
Garofalo, R. S. et al. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ. J. Clin. Invest.112, 197–208 (2003). ArticleCASPubMedPubMed Central Google Scholar
Sasaoka, T. et al. Inhibition of endogenous SHIP2 ameliorates insulin resistance caused by chronic insulin treatment in 3T3-L1 adipocytes. Diabetologia48, 336–344 (2005). ArticleCASPubMed Google Scholar
Clement, S. et al. The lipid phosphatase SHIP2 controls insulin sensitivity. Nature409, 92–97 (2001). First report of the experimental deletion of theShip2gene in mice. Although the subsequent discovery of the accidental co-disruption of a second gene (Phox2a) has introduced a complicating factor, this is still the first reported evidence for SHIP2 regulation of insulin signalingin vivo. ArticleCASPubMed Google Scholar
Clement, S. et al. corrigenda: The lipid phosphatase SHIP2 controls insulin sensitivity. Nature431, 878 (2004). ArticleCAS Google Scholar
Chiang, S. H. et al. Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature410, 944–948 (2001). ArticleCASPubMed Google Scholar
Elchebly, M. et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science283, 1544–1548 (1999). ArticleCASPubMed Google Scholar
Klaman, L. D. et al. Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol. Cell. Biol.20, 5479–5489 (2000). ArticleCASPubMedPubMed Central Google Scholar
Plum, L., Schubert, M. & Bruning, J. C. The role of insulin receptor signaling in the brain. Trends Endocrinol. Metab.16, 59–65 (2005). Concise discussion of the biology of centrally-acting insulin and its subsequent impact on whole-body energy balance, peripheral glucose homeostasis, reproduction and a potentially positive role in cognitive function and protection from neurodegenerative disease. The important role for insulin stimulation of PI3K in these activities is discussed. ArticleCASPubMed Google Scholar
Niswender, K. D. & Schwartz, M. W. Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities. Front Neuroendocrinol.24, 1–10 (2003). ArticleCASPubMed Google Scholar
Niswender, K. D., Baskin, D. G. & Schwartz, M. W. Insulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis. Trends Endocrinol. Metab.15, 362–369 (2004). ArticleCASPubMed Google Scholar
Gerozissis, K. Brain insulin and feeding: a bi-directional communication. Eur J Pharmacol490, 59–70 (2004). ArticleCASPubMed Google Scholar
Porte, D., Jr., Baskin, D. G. & Schwartz, M. W. Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans. Diabetes54, 1264–1276 (2005). Compelling and comprehensive review of the profound impact insulin signaling in the brain has on a wide range of integrated metabolic activities, including the regulation of food intake, energy expenditure, glucose homeostasis, and reproduction. In addition, evidence for cross-talk with leptin (including at the level of PI3K activation) and relevance to the known linkage between obesity and diabetes are thoughtfully explored. ArticleCASPubMed Google Scholar
Burks, D. J. et al. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature407, 377–382 (2000). ArticleCASPubMed Google Scholar
Masaki, T. et al. Obesity in insulin receptor substrate-2-deficient mice: disrupted control of arcuate nucleus neuropeptides. Obes. Res.12, 878–885 (2004). ArticleCASPubMed Google Scholar
Bruning, J. C. et al. Role of brain insulin receptor in control of body weight and reproduction. Science289, 2122–2125 (2000). ArticleCASPubMed Google Scholar
Obici, S., Feng, Z., Karkanias, G., Baskin, D. G. & Rossetti, L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nature Neurosci.5, 566–572 (2002). ArticleCASPubMed Google Scholar
Carvalheira, J. B. et al. Cross-talk between the insulin and leptin signaling systems in rat hypothalamus. Obes. Res.13, 48–57 (2005). ArticleCASPubMed Google Scholar
Rahmouni, K. et al. Hypothalamic PI3K and MAPK differentially mediate regional sympathetic activation to insulin. J. Clin. Invest.114, 652–658 (2004). ArticleCASPubMedPubMed Central Google Scholar
Fisher, S. J., Bruning, J. C., Lannon, S. & Kahn, C. R. Insulin signaling in the central nervous system is critical for the normal sympathoadrenal response to hypoglycemia. Diabetes54, 1447–1451 (2005). ArticleCASPubMed Google Scholar
Mirshamsi, S. et al. Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K dependent actin reorganization and KATP channel activation. BMC Neurosci.5, 54 (2004). ArticlePubMedPubMed CentralCAS Google Scholar
Pocai, A. et al. Hypothalamic K(ATP) channels control hepatic glucose production. Nature434, 1026–1031 (2005). ArticleCASPubMed Google Scholar
Clegg, D. J. et al. Reduced anorexic effects of insulin in obesity-prone rats fed a moderate-fat diet. Am. J. Physiol. Regul. Integr. Comp. Physiol.288, R981–R986 (2005). ArticleCASPubMed Google Scholar
De Souza, C. T. et al. Consumption of a fat-rich diet activates a pro-inflammatory response and induces insulin resistance in the hypothalamus. Endocrinology146, 4192–4199 (2005). ArticleCASPubMed Google Scholar
Lin, S., Thomas, T. C., Storlien, L. H. & Huang, X. F. Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. Int. J. Obes. Relat. Metab. Disord.24, 639–646 (2000). ArticleCASPubMed Google Scholar
Lin, L., Martin, R., Schaffhauser, A. O. & York, D. A. Acute changes in the response to peripheral leptin with alteration in the diet composition. Am. J. Physiol. Regul. Integr. Comp. Physiol.280, R504– R509 (2001). ArticleCASPubMed Google Scholar
Wilsey, J., Zolotukhin, S., Prima, V. & Scarpace, P. J. Central leptin gene therapy fails to overcome leptin resistance associated with diet-induced obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol.285, R1011– R1020 (2003). ArticleCASPubMed Google Scholar
Lu, H. et al. Obesity due to high fat diet decreases the sympathetic nervous and cardiovascular responses to intracerebroventricular leptin in rats. Brain Res. Bull.47, 331–335 (1998). ArticleCASPubMed Google Scholar
Zabolotny, J. M. et al. PTP1B regulates leptin signal transduction in vivo. Dev. Cell2, 489–95 (2002). ArticleCASPubMed Google Scholar
Cheng, A. et al. Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev. Cell2, 497–503 (2002). ArticleCASPubMed Google Scholar
Schulingkamp, R. J., Pagano, T. C., Hung, D. & Raffa, R. B. Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci. Biobehav. Rev.24, 855–872 (2000). ArticleCASPubMed Google Scholar
Tartaglia, L. A. et al. Identification and expression cloning of a leptin receptor, OB-R. Cell83, 1263–71 (1995). ArticleCASPubMed Google Scholar
Kurrimbux, D., Gaffen, Z., Farrell, C. L., Martin, D. & Thomas, S. A. The involvement of the blood-brain and the blood-cerebrospinal fluid barriers in the distribution of leptin into and out of the rat brain. Neuroscience123, 527–536 (2004). ArticleCASPubMed Google Scholar
Muraille, E. et al. The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice. Neuroscience105, 1019–1030 (2001). ArticleCASPubMed Google Scholar
Hori, H. et al. Association of SH2-containing inositol phosphatase 2 with the insulin resistance of diabetic db/db mice. Diabetes51, 2387–2394 (2002). ArticleCASPubMed Google Scholar
Fukui, K. et al. Impact of the liver-specific expression of SHIP2 (SH2-containing inositol 5′-phosphatase 2) on insulin signaling and glucose metabolism in mice. Diabetes54, 1958–1967 (2005). ArticleCASPubMed Google Scholar
Marion, E. et al. The gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for type 2 diabetes in rat and man. Diabetes51, 2012–2017 (2002). ArticleCASPubMed Google Scholar
Kaisaki, P. J. et al. Polymorphisms in type II SH2 domain-containing inositol 5-phosphatase (INPPL1, SHIP2) are associated with physiological abnormalities of the metabolic syndrome. Diabetes53, 1900–1904 (2004). ArticleCASPubMed Google Scholar
Kagawa, S. et al. Impact of SRC homology 2-containing inositol 5′-phosphatase 2 gene polymorphisms detected in a Japanese population on insulin signaling. J. Clin. Endocrinol. Metab.90, 2911–2919 (2005). ArticleCASPubMed Google Scholar
Prasad, N., Topping, R. S. & Decker, S. J. SH2-containing inositol 5′-phosphatase SHIP2 associates with the p130(Cas) adapter protein and regulates cellular adhesion and spreading. Mol. Cell. Biol.21, 1416–1428 (2001). ArticleCASPubMedPubMed Central Google Scholar
Koch, A., Mancini, A., El Bounkari, O. & Tamura, T. The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading. Oncogene24, 3436–3447 (2005). ArticleCASPubMed Google Scholar
Giuriato, S. et al. SHIP2 overexpression strongly reduces the proliferation rate of K562 erythroleukemia cell line. Biochem. Biophys. Res. Commun.296, 106–110 (2002). ArticleCASPubMed Google Scholar
Taylor, V. et al. 5′ phospholipid phosphatase SHIP-2 causes protein kinase B inactivation and cell cycle arrest in glioblastoma cells. Mol. Cell. Biol.20, 6860–6871 (2000). ArticleCASPubMedPubMed Central Google Scholar
Blero, D. et al. Phosphatidylinositol 3,4,5-trisphosphate modulation in SHIP2-deficient mouse embryonic fibroblasts. FEBS J.272, 2512–2522 (2005). ArticleCASPubMed Google Scholar
Choi, Y. et al. PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells. Oncogene21, 5289–5300 (2002). ArticleCASPubMed Google Scholar
Wisniewski, D. et al. A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP2) is constitutively tyrosine phosphorylated and associated with src homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor cells. Blood93, 2707–2720 (1999). ArticleCASPubMed Google Scholar
Helgason, C. D. et al. Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span. Genes Dev.12, 1610–1620 (1998). ArticleCASPubMedPubMed Central Google Scholar
Tsujishita, Y., Guo, S., Stolz, L. E., York, J. D. & Hurley, J. H. Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase. Cell105, 379–389 (2001). ArticleCASPubMed Google Scholar
Fisher, D. K. & Higgins, T. J. A sensitive, high-volume, colorimetric assay for protein phosphatases. Pharm. Res.11, 759–763 (1994). ArticleCASPubMed Google Scholar
Maehama, T., Taylor, G. S., Slama, J. T. & Dixon, J. E. A sensitive assay for phosphoinositide phosphatases. Anal. Biochem.279, 248–250 (2000). ArticleCASPubMed Google Scholar
Drees, B. E. et al. Competitive fluorescence polarization assays for the detection of phosphoinositide kinase and phosphatase activity. Comb. Chem. High Throughput Screen.6, 321–330 (2003). ArticleCASPubMed Google Scholar
Gray, A., Olsson, H., Batty, I. H., Priganica, L. & Peter Downes, C. Nonradioactive methods for the assay of phosphoinositide 3-kinases and phosphoinositide phosphatases and selective detection of signaling lipids in cell and tissue extracts. Anal. Biochem.313, 234–245 (2003). ArticleCASPubMed Google Scholar
Oatey, P. B. et al. Confocal imaging of the subcellular distribution of phosphatidylinositol 3,4,5-trisphosphate in insulin- and PDGF-stimulated 3T3-L1 adipocytes. Biochem. J.344, 511–518 (1999). ArticleCASPubMedPubMed Central Google Scholar
Sato, M., Ueda, Y., Takagi, T. & Umezawa, Y. Production of PtdInsP3 at endomembranes is triggered by receptor endocytosis. Nature Cell. Biol.5, 1016–1022 (2003). One of several recent reports demonstrating novel approaches for the measurement of PtdIns(3,4,5)P3levels in biological samples. The FRET-based biosensor approach utilized in this study is noteworthy for the ability to continuously monitor PtdIns(3,4,5)P3levels in living cells and in specific subcellular compartments. ArticleCASPubMed Google Scholar
Tengholm, A., Teruel, M. N. & Meyer, T. Single cell imaging of PI3K activity and glucose transporter insertion into the plasma membrane by dual color evanescent wave microscopy. Sci STKE2003, PL4 (2003). ArticlePubMed Google Scholar
Niswender, K. D. et al. Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptin. J. Histochem. Cytochem.51, 275–283 (2003). ArticleCASPubMed Google Scholar
Wiesmann, C. et al. Allosteric inhibition of protein tyrosine phosphatase 1B. Nature Struct. Mol. Biol.11, 730–737 (2004). ArticleCAS Google Scholar
Yang, L. et al. Synthesis of pelorol and analogues: activators of the inositol 5-phosphatase SHIP. Org. Lett.7, 1073–1076 (2005). ArticleCASPubMed Google Scholar