PI3K-C2γ 3 is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling (232 views)
Nat Commun (ISSN: 2041-1723, 2041-1723electronic, 2041-1723linking), 2015; 6: N/D-N/D.
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Paper type: Journal Article,
Impact factor: 11.329, 5-year impact factor: 12.001
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930184555&doi=10.1038%2fncomms8400&partnerID=40&md5=55121934fe26faa6c6a98467b7cdda79
Keywords: Foxo2 Protein, Foxo3 Protein, Glycogen, Insulin, Isoenzyme, Phosphatidylinositol 3 Kinase, Phosphatidylinositol 3 Kinase C2 Gamma, 4 Bisphosphate, Protein Kinase B Beta, Rab Protein, Transcription Factor, Transcription Factor Fkhr, Unclassified Drug, Akt1 Protein, Mouse, Akt2 Protein, Forkhead Transcription Factor, Glucose, Glycogen Synthase, 4-Diphosphate, Pik3c2g Protein, Polyphosphoinositide, S6 Kinase, Enzyme Activity, Germ Cell, Homeostasis, Membrane, Metabolism, Signaling, Animal Cell, Animal Experiment, Animal Model, Animal Tissue, Article, Controlled Study, Endosome, Female, Glucose Homeostasis, Hyperlipidemia, Insulin Resistance, Lipid Diet, Liver, Nonhuman, Obesity, Signal Transduction, Aging, C57bl Mouse, Genetics, Knockout Mouse, Liver Cell, Adiposity, High-Fat, Hepatocytes, Inbred C57bl, Phosphatidylinositol 3-Kinases, Phosphatidylinositol Phosphates, Proto-Oncogene Proteins C-Akt, Rab5 Gtp-Binding Proteins, Ribosomal Protein S6 Kinases,
Affiliations:
*** IBB - CNR ***
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, 10126, Italy
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, 20133, Italy
INSERM, 1 av Jean-Poulhes, Toulouse, 31432, France
Metabolic Signalling Group, School of Biomedical Sciences, Curtin University, Perth, WA 6102, Australia
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, CH-1015, Switzerland
Institute of Biostructure and Bioimaging, Molecular Biotechnology Center, University of Torino, Torino, 10126, Italy
Beth Israel Deaconess Medical Center, Harvard, Boston, MA 02215, United States
References:
Fayard, E., Xue, G., Parcellier, A., Bozulic, L., Hemmings, B.A., Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway (2010) Curr. Top. Microbiol. Immunol., 346, pp. 31-5
Taniguchi, C.M., Emanuelli, B., Kahn, C.R., Critical nodes in signalling pathways: Insights into insulin action (2006) Nat. Rev. Mol. Cell Biol., 7, pp. 85-96
Foukas, L.C., Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation (2006) Nature, 441, pp. 366-370
Khan, M.N., Internalization and activation of the rat liver insulin receptor kinase in vivo (1989) J. Biol. Chem., 264, pp. 12931-12940
Su, X., Lodhi, I.J., Saltiel, A.R., Stahl, P.D., Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5 (2006) J. Biol. Chem., 281, pp. 27982-27990
Cheng, K.K., APPL1 potentiates insulin-mediated inhibition of hepatic glucose production and alleviates diabetes via Akt activation in mice (2009) Cell Metab., 9, pp. 417-427
Ciraolo, E., Phosphoinositide 3-kinase p110beta activity: Key role in metabolism and mammary gland cancer but not development (2008) Sci. Signal, 1, p. ra3
Jia, S., Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis (2008) Nature, 454, pp. 776-779
Christoforidis, S., Phosphatidylinositol-3-OH kinases are Rab5 effectors (1999) Nat. Cell Biol., 1, pp. 249-252
Shin, H.W., An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway (2005) J. Cell Biol., 170, pp. 607-618
Falasca, M., Maffucci, T., Rethinking phosphatidylinositol 3-monophosphate (2009) Biochim. Biophys. Acta, 1793, pp. 1795-1803
Zoncu, R., A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes (2009) Cell, 136, pp. 1110-1121
Ivetac, I., The type Ialpha inositol polyphosphate 4-phosphatase generates and terminates phosphoinositide 3-kinase signals on endosomes and the plasma membrane (2005) Mol. Biol. Cell, 16, pp. 2218-2233
Posor, Y., Spatiotemporal control of endocytosis by phosphatidylinositol-3, 4-bisphosphate (2013) Nature, 499, pp. 233-237
Falasca, M., The role of phosphoinositide 3-kinase C2alpha in insulin signaling (2007) J. Biol. Chem., 282, pp. 28226-28236
Campa, C.C., Franco, I., Hirsch, E., PI3K-C2a: One enzyme for two products coupling vesicle trafficking and signal transduction FEBS Lett, pp. S0014-5793
Dominguez, V., Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells (2011) J. Biol. Chem., 286, pp. 4216-4225
Franco, I., PI3K class II a controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function (2014) Dev. Cell, 28, pp. 647-658
Arcaro, A., Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors (2000) Mol. Cell Biol., 20, pp. 3817-3830
Brown, R.A., Domin, J., Arcaro, A., Waterfield, M.D., Shepherd, P.R., Insulin activates the alpha isoform of class II phosphoinositide 3-kinase (1999) J. Biol. Chem., 274, pp. 14529-14532
Harada, K., Truong, A.B., Cai, T., Khavari, P.A., The class II phosphoinositide 3-kinase C2beta is not essential for epidermal differentiation (2005) Mol. Cell Biol., 25, pp. 11122-11130
Ho, L.K., Liu, D., Rozycka, M., Brown, R.A., Fry, M.J., Identification of four novel human phosphoinositide 3-kinases defines a multi-isoform subfamily (1997) Biochem. Biophys. Res. Commun., 235, pp. 130-137
Rozycka, M., CDNA cloning of a third human C2-domain-containing class II phosphoinositide 3-kinase, PI3K-C2gamma, and chromosomal assignment of this gene (PIK3C2G) to 12p12 (1998) Genomics, 54, pp. 569-574
Misawa, H., Cloning and characterization of a novel class II phosphoinositide 3-kinase containing C2 domain (1998) Biochem. Biophys. Res. Commun., 244, pp. 531-539
Daimon, M., Association of the PIK3C2G gene polymorphisms with type 2 DM in a Japanese population (2008) Biochem. Biophys. Res. Commun., 365, pp. 466-471
Crosson, S.M., Khan, A., Printen, J., Pessin, J.E., Saltiel, A.R., PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance (2003) J. Clin. Invest., 111, pp. 1423-1432
Lu, M., Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1 (2012) Nature Med., 18, pp. 388-395
Wan, M., A noncanonical GSK3-independent pathway controls postprandial hepatic glycogen deposition (2013) Cell Metab., 18, pp. 99-105
Leavens, K.F., Birnbaum, M.J., Insulin signaling to hepatic lipid metabolism in health and disease (2011) Crit. Rev. Biochem. Mol. Biol., 46, pp. 200-215
Scheid, M.P., Phosphatidylinositol (3, 4, 5)P3 is essential but not sufficient for protein kinase B (PKB) activation
Murray, J.T., Backer, J.M., Analysis of hVps34/hVps15 interactions with Rab5 in vivo and in vitro (2005) Methods Enzymol., 403, pp. 789-799
Von Wilamowitz-Moellendorff, A., Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis (2013) Diabetes, 62, pp. 4070-4082
Schutz, Y., Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis (2004) Int. J. Obes. Relat. Metab. Disord., 28, pp. S3-S11
Bruning, J.C., A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance (1998) Mol. Cell, 2, pp. 559-569
Kim, J.K., Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle (2000) J. Clin. Invest., 105, pp. 1791-1797
Sopasakis, V.R., Specific roles of the p110alpha isoform of phosphatidylinsositol 3-kinase in hepatic insulin signaling and metabolic regulation (2010) Cell Metab., 11, pp. 220-230
Saltiel, A.R., Pessin, J.E., Insulin signaling pathways in time and space (2002) Trends Cell Biol., 12, pp. 65-71
Von Zastrow, M., Sorkin, A., Signaling on the endocytic pathway (2007) Curr. Opin. Cell Biol., 19, pp. 436-445
Zhao, S., Guan, K.L., Substrate selectivity APPLies to Akt (2008) Cell, 133, pp. 399-400
Scita, G., Di Fiore, P.P., The endocytic matrix (2010) Nature, 463, pp. 464-473
Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., Bilanges, B., The emerging mechanisms of isoform-specific PI3K signalling (2010) Nat. Rev. Mol. Cell Biol., 11, pp. 329-341
Ivetac, I., Regulation of PI(3)K/Akt signalling and cellular transformation by inositol polyphosphate 4-phosphatase-1 (2009) EMBO Rep., pp. 487-493
Zeigerer, A., Rab5 is necessary for the biogenesis of the endolysosomal system in vivo (2012) Nature, 485, pp. 465-470
Lodhi, I.J., Insulin stimulates phosphatidylinositol 3-phosphate production via the activation of Rab5 (2008) Mol. Biol. Cell, 19, pp. 2718-2728
Miaczynska, M., APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment (2004) Cell, 116, pp. 445-456
Schenck, A., The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development (2008) Cell, 133, pp. 486-497
Mitsuuchi, Y., Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2 (1999) Oncogene, 18, pp. 4891-4898
Saito, T., Jones, C.C., Huang, S., Czech, M.P., Pilch, P.F., The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation (2007) J. Biol. Chem., 282, pp. 32280-32287
Semple, R.K., Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis (2009) J. Clin. Invest., 119, pp. 315-322
Leavens, K.F., Easton, R.M., Shulman, G.I., Previs, S.F., Birnbaum, M.J., Akt2 is required for hepatic lipid accumulation in models of insulin resistance (2009) Cell Metab., 10, pp. 405-418
Cho, H., Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta) (2001) Science, 292, pp. 1728-1731
Mora, A., Lipina, C., Tronche, F., Sutherland, C., Alessi, D.R., Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure (2005) Biochem. J., 385, pp. 639-648
Balla, T., Varnai, P., Visualization of cellular phosphoinositide pools with GFP-fused protein-domains (2009) Curr. Protoc. Cell Biol., , Chapter 24 Unit 24
Thomas, J.A., Schlender, K.K., Larner, J., A rapid filter paper assay for UDPglucose-glycogen glucosyltransferase, including an improved biosynthesis of UDP-14C-glucose (1968) Anal. Biochem., 25, pp. 486-499
Fritsch, R., RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms (2013) Cell, 153, pp. 1050-1063
Goncalves, L.A., Vigario, A.M., Penha-Goncalves, C., Improved isolation of murine hepatocytes for in vitro malaria liver stage studies (2007) Malar. J., 6, p. 169
Nat Commun (ISSN: 2041-1723, 2041-1723electronic, 2041-1723linking), 2015; 6: N/D-N/D.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 11.329, 5-year impact factor: 12.001
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930184555&doi=10.1038%2fncomms8400&partnerID=40&md5=55121934fe26faa6c6a98467b7cdda79
Keywords: Foxo2 Protein, Foxo3 Protein, Glycogen, Insulin, Isoenzyme, Phosphatidylinositol 3 Kinase, Phosphatidylinositol 3 Kinase C2 Gamma, 4 Bisphosphate, Protein Kinase B Beta, Rab Protein, Transcription Factor, Transcription Factor Fkhr, Unclassified Drug, Akt1 Protein, Mouse, Akt2 Protein, Forkhead Transcription Factor, Glucose, Glycogen Synthase, 4-Diphosphate, Pik3c2g Protein, Polyphosphoinositide, S6 Kinase, Enzyme Activity, Germ Cell, Homeostasis, Membrane, Metabolism, Signaling, Animal Cell, Animal Experiment, Animal Model, Animal Tissue, Article, Controlled Study, Endosome, Female, Glucose Homeostasis, Hyperlipidemia, Insulin Resistance, Lipid Diet, Liver, Nonhuman, Obesity, Signal Transduction, Aging, C57bl Mouse, Genetics, Knockout Mouse, Liver Cell, Adiposity, High-Fat, Hepatocytes, Inbred C57bl, Phosphatidylinositol 3-Kinases, Phosphatidylinositol Phosphates, Proto-Oncogene Proteins C-Akt, Rab5 Gtp-Binding Proteins, Ribosomal Protein S6 Kinases,
Affiliations:
*** IBB - CNR ***
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, 10126, Italy
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, 20133, Italy
INSERM, 1 av Jean-Poulhes, Toulouse, 31432, France
Metabolic Signalling Group, School of Biomedical Sciences, Curtin University, Perth, WA 6102, Australia
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, CH-1015, Switzerland
Institute of Biostructure and Bioimaging, Molecular Biotechnology Center, University of Torino, Torino, 10126, Italy
Beth Israel Deaconess Medical Center, Harvard, Boston, MA 02215, United States
References:
Fayard, E., Xue, G., Parcellier, A., Bozulic, L., Hemmings, B.A., Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway (2010) Curr. Top. Microbiol. Immunol., 346, pp. 31-5
Taniguchi, C.M., Emanuelli, B., Kahn, C.R., Critical nodes in signalling pathways: Insights into insulin action (2006) Nat. Rev. Mol. Cell Biol., 7, pp. 85-96
Foukas, L.C., Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation (2006) Nature, 441, pp. 366-370
Khan, M.N., Internalization and activation of the rat liver insulin receptor kinase in vivo (1989) J. Biol. Chem., 264, pp. 12931-12940
Su, X., Lodhi, I.J., Saltiel, A.R., Stahl, P.D., Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5 (2006) J. Biol. Chem., 281, pp. 27982-27990
Cheng, K.K., APPL1 potentiates insulin-mediated inhibition of hepatic glucose production and alleviates diabetes via Akt activation in mice (2009) Cell Metab., 9, pp. 417-427
Ciraolo, E., Phosphoinositide 3-kinase p110beta activity: Key role in metabolism and mammary gland cancer but not development (2008) Sci. Signal, 1, p. ra3
Jia, S., Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis (2008) Nature, 454, pp. 776-779
Christoforidis, S., Phosphatidylinositol-3-OH kinases are Rab5 effectors (1999) Nat. Cell Biol., 1, pp. 249-252
Shin, H.W., An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway (2005) J. Cell Biol., 170, pp. 607-618
Falasca, M., Maffucci, T., Rethinking phosphatidylinositol 3-monophosphate (2009) Biochim. Biophys. Acta, 1793, pp. 1795-1803
Zoncu, R., A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes (2009) Cell, 136, pp. 1110-1121
Ivetac, I., The type Ialpha inositol polyphosphate 4-phosphatase generates and terminates phosphoinositide 3-kinase signals on endosomes and the plasma membrane (2005) Mol. Biol. Cell, 16, pp. 2218-2233
Posor, Y., Spatiotemporal control of endocytosis by phosphatidylinositol-3, 4-bisphosphate (2013) Nature, 499, pp. 233-237
Falasca, M., The role of phosphoinositide 3-kinase C2alpha in insulin signaling (2007) J. Biol. Chem., 282, pp. 28226-28236
Campa, C.C., Franco, I., Hirsch, E., PI3K-C2a: One enzyme for two products coupling vesicle trafficking and signal transduction FEBS Lett, pp. S0014-5793
Dominguez, V., Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells (2011) J. Biol. Chem., 286, pp. 4216-4225
Franco, I., PI3K class II a controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function (2014) Dev. Cell, 28, pp. 647-658
Arcaro, A., Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors (2000) Mol. Cell Biol., 20, pp. 3817-3830
Brown, R.A., Domin, J., Arcaro, A., Waterfield, M.D., Shepherd, P.R., Insulin activates the alpha isoform of class II phosphoinositide 3-kinase (1999) J. Biol. Chem., 274, pp. 14529-14532
Harada, K., Truong, A.B., Cai, T., Khavari, P.A., The class II phosphoinositide 3-kinase C2beta is not essential for epidermal differentiation (2005) Mol. Cell Biol., 25, pp. 11122-11130
Ho, L.K., Liu, D., Rozycka, M., Brown, R.A., Fry, M.J., Identification of four novel human phosphoinositide 3-kinases defines a multi-isoform subfamily (1997) Biochem. Biophys. Res. Commun., 235, pp. 130-137
Rozycka, M., CDNA cloning of a third human C2-domain-containing class II phosphoinositide 3-kinase, PI3K-C2gamma, and chromosomal assignment of this gene (PIK3C2G) to 12p12 (1998) Genomics, 54, pp. 569-574
Misawa, H., Cloning and characterization of a novel class II phosphoinositide 3-kinase containing C2 domain (1998) Biochem. Biophys. Res. Commun., 244, pp. 531-539
Daimon, M., Association of the PIK3C2G gene polymorphisms with type 2 DM in a Japanese population (2008) Biochem. Biophys. Res. Commun., 365, pp. 466-471
Crosson, S.M., Khan, A., Printen, J., Pessin, J.E., Saltiel, A.R., PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance (2003) J. Clin. Invest., 111, pp. 1423-1432
Lu, M., Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1 (2012) Nature Med., 18, pp. 388-395
Wan, M., A noncanonical GSK3-independent pathway controls postprandial hepatic glycogen deposition (2013) Cell Metab., 18, pp. 99-105
Leavens, K.F., Birnbaum, M.J., Insulin signaling to hepatic lipid metabolism in health and disease (2011) Crit. Rev. Biochem. Mol. Biol., 46, pp. 200-215
Scheid, M.P., Phosphatidylinositol (3, 4, 5)P3 is essential but not sufficient for protein kinase B (PKB) activation
Murray, J.T., Backer, J.M., Analysis of hVps34/hVps15 interactions with Rab5 in vivo and in vitro (2005) Methods Enzymol., 403, pp. 789-799
Von Wilamowitz-Moellendorff, A., Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis (2013) Diabetes, 62, pp. 4070-4082
Schutz, Y., Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis (2004) Int. J. Obes. Relat. Metab. Disord., 28, pp. S3-S11
Bruning, J.C., A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance (1998) Mol. Cell, 2, pp. 559-569
Kim, J.K., Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle (2000) J. Clin. Invest., 105, pp. 1791-1797
Sopasakis, V.R., Specific roles of the p110alpha isoform of phosphatidylinsositol 3-kinase in hepatic insulin signaling and metabolic regulation (2010) Cell Metab., 11, pp. 220-230
Saltiel, A.R., Pessin, J.E., Insulin signaling pathways in time and space (2002) Trends Cell Biol., 12, pp. 65-71
Von Zastrow, M., Sorkin, A., Signaling on the endocytic pathway (2007) Curr. Opin. Cell Biol., 19, pp. 436-445
Zhao, S., Guan, K.L., Substrate selectivity APPLies to Akt (2008) Cell, 133, pp. 399-400
Scita, G., Di Fiore, P.P., The endocytic matrix (2010) Nature, 463, pp. 464-473
Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., Bilanges, B., The emerging mechanisms of isoform-specific PI3K signalling (2010) Nat. Rev. Mol. Cell Biol., 11, pp. 329-341
Ivetac, I., Regulation of PI(3)K/Akt signalling and cellular transformation by inositol polyphosphate 4-phosphatase-1 (2009) EMBO Rep., pp. 487-493
Zeigerer, A., Rab5 is necessary for the biogenesis of the endolysosomal system in vivo (2012) Nature, 485, pp. 465-470
Lodhi, I.J., Insulin stimulates phosphatidylinositol 3-phosphate production via the activation of Rab5 (2008) Mol. Biol. Cell, 19, pp. 2718-2728
Miaczynska, M., APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment (2004) Cell, 116, pp. 445-456
Schenck, A., The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development (2008) Cell, 133, pp. 486-497
Mitsuuchi, Y., Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2 (1999) Oncogene, 18, pp. 4891-4898
Saito, T., Jones, C.C., Huang, S., Czech, M.P., Pilch, P.F., The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation (2007) J. Biol. Chem., 282, pp. 32280-32287
Semple, R.K., Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis (2009) J. Clin. Invest., 119, pp. 315-322
Leavens, K.F., Easton, R.M., Shulman, G.I., Previs, S.F., Birnbaum, M.J., Akt2 is required for hepatic lipid accumulation in models of insulin resistance (2009) Cell Metab., 10, pp. 405-418
Cho, H., Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta) (2001) Science, 292, pp. 1728-1731
Mora, A., Lipina, C., Tronche, F., Sutherland, C., Alessi, D.R., Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure (2005) Biochem. J., 385, pp. 639-648
Balla, T., Varnai, P., Visualization of cellular phosphoinositide pools with GFP-fused protein-domains (2009) Curr. Protoc. Cell Biol., , Chapter 24 Unit 24
Thomas, J.A., Schlender, K.K., Larner, J., A rapid filter paper assay for UDPglucose-glycogen glucosyltransferase, including an improved biosynthesis of UDP-14C-glucose (1968) Anal. Biochem., 25, pp. 486-499
Fritsch, R., RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms (2013) Cell, 153, pp. 1050-1063
Goncalves, L.A., Vigario, A.M., Penha-Goncalves, C., Improved isolation of murine hepatocytes for in vitro malaria liver stage studies (2007) Malar. J., 6, p. 169
PI3K-C2γ 3 is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling
In the liver, insulin-mediated activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is at the core of metabolic control. Multiple PI3K and Akt isoenzymes are found in hepatocytes and whether isoform-selective interplays exist is currently unclear. Here we report that insulin signalling triggers the association of the liver-specific class II PI3K isoform γ (PI3K-C2γ) with Rab5-GTP, and its recruitment to Rab5-positive early endosomes. In these vesicles, PI3K-C2γ produces a phosphatidylinositol-3,4-bisphosphate pool specifically required for delayed and sustained endosomal Akt2 stimulation. Accordingly, loss of PI3K-C2γ does not affect insulin-dependent Akt1 activation as well as S6K and FoxO1-3 phosphorylation, but selectively reduces Akt2 activation, which specifically inhibits glycogen synthase activity. As a consequence, PI3K-C2γ-deficient mice display severely reduced liver accumulation of glycogen and develop hyperlipidemia, adiposity as well as insulin resistance with age or after consumption of a high-fat diet. Our data indicate PI3K-C2γ supports an isoenzyme-specific forking of insulin-mediated signal transduction to an endosomal pool of Akt2, required for glucose homeostasis.
In the liver, insulin-mediated activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is at the core of metabolic control. Multiple PI3K and Akt isoenzymes are found in hepatocytes and whether isoform-selective interplays exist is currently unclear. Here we report that insulin signalling triggers the association of the liver-specific class II PI3K isoform γ (PI3K-C2γ) with Rab5-GTP, and its recruitment to Rab5-positive early endosomes. In these vesicles, PI3K-C2γ produces a phosphatidylinositol-3,4-bisphosphate pool specifically required for delayed and sustained endosomal Akt2 stimulation. Accordingly, loss of PI3K-C2γ does not affect insulin-dependent Akt1 activation as well as S6K and FoxO1-3 phosphorylation, but selectively reduces Akt2 activation, which specifically inhibits glycogen synthase activity. As a consequence, PI3K-C2γ-deficient mice display severely reduced liver accumulation of glycogen and develop hyperlipidemia, adiposity as well as insulin resistance with age or after consumption of a high-fat diet. Our data indicate PI3K-C2γ supports an isoenzyme-specific forking of insulin-mediated signal transduction to an endosomal pool of Akt2, required for glucose homeostasis.
PI3K-C2γ 3 is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling
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PI3K-C2γ 3 is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling
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J Neurosci (ISSN: 1529-2401, 0270-6474), 2009 Sep 26; 29(34): 10582-10587.
Impact Factor: 3.669
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Caraci F, Battaglia G, Busceti C, Biagioni F, Mastroiacovo F, Bosco P, Drago F, Nicoletti F, Sortino MA, Copani A
* TGF-β1 protects against Aβ-neurotoxicity via the phosphatidylinositol-3-kinase pathway (440 views)
Neurobiology Of Disease (ISSN: 0969-9961), 2008 May; 30(2): 234-242.
Impact Factor: 4.852
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Fiory F, Alberobello AT, Miele C, Oriente F, Esposito I, Corbo V, Ruvo M, Tizzano B, Rasmussen TE, Gammeltoft S, Formisano P, Beguinot F
* Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 by the insulin receptor is necessary for insulin metabolic signaling (462 views)
Mol Cell Biol (ISSN: 0270-7306, 1098-5549), 2005 Dec; 25(24): 10803-10814.
Impact Factor: 7.093
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Iaccarino G, Ciccarelli M, Sorriento D, Galasso G, Campanile A, Santulli G, Cipolletta E, Cerullo V, Cimini V, Altobelli GG, Piscione F, Priante O, Pastore L, Chiariello M, Salvatore F, Koch WJ, Trimarco B
* Ischemic neoangiogenesis enhanced by β2-adrenergic receptor overexpression: A novel role for the endothelial adrenergic system (380 views)
Circ Res (ISSN: 0009-7330, 1524-4571electronic), 2005; 97(11): 1182-1189.
Impact Factor: 9.408
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* Radioresistance in head and neck squamous cell carcinoma: Biological bases and therapeutic implications (524 views)
Head Neck-J Sci Spec (ISSN: 1043-3074), 2015; 37(5): 763-770.
Impact Factor: 2.76
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Mercurio FA, Scognamiglio PL, Di Natale C, Marasco D, Pellecchia M, Leone M
* Cd And Nmr Conformational Studies Of A Peptide Encompassing The Mid Loop Interface Of Ship2-Sam (349 views)
Biopolymers (ISSN: 0006-3525, 0006-6352, 0006-3525print), 2014 Nov; 101(11): 1088-1098.
Impact Factor: 2.385
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Mercurio FA, Marasco D, Pirone L, Scognamiglio PL, Pedone E, Pellecchia M, Leone M
* Heterotypic Sam-Sam Association Between Odin-Sam1 And Arap3-Sam: Binding Affinity And Structural Insights (402 views)
Chembiochem (ISSN: 1439-4227, 1439-9422, 1439-7633), 2013 Jan 2; 14(1): 100-106.
Impact Factor: 2.92
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Tedesco I, Russo M, Bilotto S, Spagnuolo C, Scognamiglio A, Palumbo R, Nappo A, Iacomino G, Moio L, Russo GL
* Dealcoholated red wine induces autophagic and apoptotic cell death in an osteosarcoma cell line (546 views)
Food Chem Toxicol (ISSN: 0278-6915), 2013; 60: 377-384.
Impact Factor: 2.61
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Folgiero V, Di Carlo SE, Bossi G, Spugnini E, Di Benedetto A, Bon G, Milella M, Fabi A, Accardo A, Morelli G, Mottolese M, Falcioni R
* Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast cancer cells (519 views)
Cell Death & (ISSN: 2041-4889, 2041-4889electronic), 2012; 3(12): N/D-N/D.
Impact Factor: 6.044
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Giuffrida ML, Caraci F, Pignataro B, Cataldo S, De Bona P, Bruno V, Molinaro G, Pappalardo G, Messina A, Palmigiano A, Garozzo D, Nicoletti F, Rizzarelli E, Copani A
* Beta-Amyloid Monomers Are Neuroprotective (708 views)
J Neurosci (ISSN: 1529-2401, 0270-6474), 2009 Sep 26; 29(34): 10582-10587.
Impact Factor: 3.669
View Export to BibTeX Export to EndNote
Caraci F, Battaglia G, Busceti C, Biagioni F, Mastroiacovo F, Bosco P, Drago F, Nicoletti F, Sortino MA, Copani A
* TGF-β1 protects against Aβ-neurotoxicity via the phosphatidylinositol-3-kinase pathway (440 views)
Neurobiology Of Disease (ISSN: 0969-9961), 2008 May; 30(2): 234-242.
Impact Factor: 4.852
View Export to BibTeX Export to EndNote
Fiory F, Alberobello AT, Miele C, Oriente F, Esposito I, Corbo V, Ruvo M, Tizzano B, Rasmussen TE, Gammeltoft S, Formisano P, Beguinot F
* Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 by the insulin receptor is necessary for insulin metabolic signaling (462 views)
Mol Cell Biol (ISSN: 0270-7306, 1098-5549), 2005 Dec; 25(24): 10803-10814.
Impact Factor: 7.093
View Export to BibTeX Export to EndNote
Iaccarino G, Ciccarelli M, Sorriento D, Galasso G, Campanile A, Santulli G, Cipolletta E, Cerullo V, Cimini V, Altobelli GG, Piscione F, Priante O, Pastore L, Chiariello M, Salvatore F, Koch WJ, Trimarco B
* Ischemic neoangiogenesis enhanced by β2-adrenergic receptor overexpression: A novel role for the endothelial adrenergic system (380 views)
Circ Res (ISSN: 0009-7330, 1524-4571electronic), 2005; 97(11): 1182-1189.
Impact Factor: 9.408
View Export to BibTeX Export to EndNote
9 Records (8 excluding Abstracts).
Total impact factor: 41.741 (35.697 excluding Abstracts).
Total 5 year impact factor: 43.363 (37.319 excluding Abstracts).
Total impact factor: 41.741 (35.697 excluding Abstracts).
Total 5 year impact factor: 43.363 (37.319 excluding Abstracts).
232 views. Last view on Thursday 01 June 2023, 2:32:12
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