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GRK 1302:  The PI3K Pathway in Tumour Growth and Diabetes

Subject Area Medicine
Term from 2006 to 2015
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 12447501
 
Final Report Year 2017

Final Report Abstract

Phosphatidylinositol-3-kinase (PI3K) regulates crucial biological processes including cell survival, apoptosis, autophagy, metabolism and cell migration. Alterations of this central pathway are essentially involved in tumorigenesis. PI3K controls also nutrient uptake and cellular metabolism and thereby plays an important role in the pathogenesis of diabetes. Understanding this complexity of PI3K signaling necessitates broad interdisciplinary approaches in order to successfully address the urgent questions of this research field and to open up new possibilities for therapeutic intervention. The research goal of the iRTG-1302 was to study novel aspects of the PI3K signaling path-way and its contribution to tumor growth and diabetes, with a particular emphasis in exploring common themes and cross-talks involved in both pathologies. In addition, a training goal was to provide broad and modern education to doctoral students in cancer and diabetes research by combining innovative approaches in an interdisciplinary way. To this end, an interactive network was established combining Tübingen's expertise in tumor biology, physiology, cell biology, molecular medicine, pharmacology, clinical oncology and diabetology with the University of Dundee and its expertise in protein phosphorylation, kinase signaling and mouse genetics. The scientific surplus value of the mutual interaction between Tübingen and Dundee relied in the complementation of a genuine expertise. Students of the IRTR-1302 clearly benefitted from the truly interdisciplinary expertise. The integrated training and qualification program allowed them to gain an outstanding research qualification in the various disciplines. Moreover, the temporary exchange of students with the partner laboratories and excellent research facilities at both sites provided the students with additional know-how of modern techniques and allowed them to perform their interdisciplinary research projects on a clearly international level. By this way, a total of 42 funded and associated students were supported by the iRTG-1302, many of whom subsequently found excellent research positions in academia or industry. The IRTG was also highly successful from a scientific point of view. PI3K is typically activated by receptor tyrosine kinases, such as the insulin receptor, or G-protein-coupled receptors. Following this event, PI3K activates various downstream effector kinases such as PDK1, AKT and SGK. The iRTG-1302 has contributed significantly to a further understanding of PI3K signaling by identifying new kinase substrates and downstream targets, including other kinases, ion channels, transport molecules and transcription factors. Projects of the iRTG-1302 also elucidated novel upstream regulatory events in PI3K/PDK1 signaling as well as novel loops in the intense crosstalk between PI3K and the RAS/MAPK pathway. Moreover, a deeper understanding of the role of PI3K signaling in fundamental processes, such as apoptosis, senescence and autophagy, was gained by the iRTG. By controlling these processes in both diabetes and cancer, dysregulation of PI3K was found to crucially regulate drug and insulin resistance in both normal and transformed cells. Drugs targeting the PI3K pathway have emerged as highly promising tumor treatments. Indeed, during the course of this IRTG PI3K signaling emerged as a principal control pathway of metabolic reprograming and proliferation processes, which has recently opened up unexpected new mechanistic links between inflammation, obesity and cancer formation. Based on the success of the iRTG, Tübingen has therefore initiated several new research networks studying these links between metabolism, the microbiome and malignancy.

Publications

  • (2009) Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo. Mol Cancer 8:114
    Gu S, Papadopoulou N, Gehring EM, Nasir O, Dimas K, Bhavsar SK, Föller M, Alevizopoulos K, Lang F, Stournaras C
    (See online at https://doi.org/10.1186/1476-4598-8-114)
  • (2009) Gβ-copurified lipid kinase impurity from Sf9 cells. Protein Pept Lett 16:1053-1056
    Shymanets A, Ahmadian MR, Nürnberg B
    (See online at https://dx.doi.org/10.2174/092986609789055340)
  • (2009) Modulation of suicidal erythrocyte cation channels by an AMPA antagonist. J Cell Mol Med 13:3680-3686
    Föller M, Mahmud H, Gu S, Kucherenko Y, Gehring EM, Shumilina E, Floride E, Sprengel R, Lang F
    (See online at https://doi.org/10.1111/j.1582-4934.2009.00745.x)
  • (2009) PIKfyve upregulates CFTR activity. Biochem Biophys Res Commun 390:952-957
    Gehring EM, Lam RS, Siraskar G, Koutsouki E, Seebohm G, Ureche ON, Ureche L, Baltaev R, Tavare JM, Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2009.10.084)
  • (2009) PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3. Psychopharmacology (Berl) 206:429-435
    Fedorenko O, Tang C, Sopjani M, Föller M, Gehring EM, Strutz-Seebohm N, Ureche ON, Ivanova S, Semke A, Lang F, Seebohm G, Lang UE
    (See online at https://doi.org/10.1007/s00213-009-1621-5)
  • (2009) Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110?. Proc Natl Acad Sci USA 106:20312-20317
    Kurig B, Shymanets A, Bohnacker T, Prajwal, Brock C, Ahmadian MR, Schaefer M, Gohla A, Harteneck C, Wymann MP, Jeanclos E, Nürnberg B
    (See online at https://doi.org/10.1073/pnas.0905506106)
  • (2009) Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110γ. Proc Natl Acad Sci USA 106:20312-20317
    Kurig B, Shymanets A, Bohnacker T, Prajwal, Brock C, Ahmadian MR, Schaefer M, Gohla A, Harteneck C, Wymann MP, Jeanclos E, Nürnberg B
    (See online at https://doi.org/10.1073/pnas.0905506106)
  • (2009) Regulation of the glutamate transporter EAAT2 by PIKfyve. Cell Physiol Biochem 24:361-368
    Gehring EM, Zürn A, Klaus F, Laufer J, Sopjani M, Lindner R, Strutz-Seebohm N, Tavaré JM, Boehmer C, Palmada M, Lang UE, Seebohm G, Lang F
    (See online at https://doi.org/10.1159/000257428)
  • (2009) Regulation of the Na+- coupled glutamate transporter EAAT3 by PIKfyve. Neurochem Int 54:372-377
    Klaus F, Gehring EM, Zürn A, Laufer J, Lindner R, Strutz-Seebohm N, Tavaré JM, Rothstein JD, Boehmer C, Palmada M, Gruner I, Lang UE, Seebohm G, Lang F
    (See online at https://doi.org/10.1016/j.neuint.2009.01.002)
  • (2009) Stimulation of electrogenic intestinal dipeptide transport by the glucocorticoid dexamethasone. Pflugers Arch 459:191-202
    Rexhepaj R, Dërmaku-Sopjani M, Gehring EM, Sopjani M, Kempe DS, Föller M, Lang F
    (See online at https://doi.org/10.1159/000322331)
  • (2010) Hyperaldosteronism in Klotho-deficient mice. Am J Physiol Renal Physiol 5:F1171-F1177
    Fischer SS, Kempe DS, Leibrock C, Rexhepaj R, Siraskar B, Boini KM, Ackermann TF, Föller M, Hocher B, Rosenblatt KP, Kuro-O M, Lang F
    (See online at https://doi.org/10.1152/ajprenal.00233.2010)
  • (2010) Inhibition of voltage-gated K+ channels in dendritic cells by rapamycin. Am J Physiol - Cell Physiol 299:C1379-C1385
    Tyan L, Sopjani M, Dërmaku-Sopjani M, Schmid E, Yang W, Xuan NT, Shumilina E, Lang F
    (See online at https://doi.org/10.1152/ajpcell.00367.2010)
  • (2010) Inhibition of voltage-gated K+ channels in dendritic cells by rapamycin. Am J Physiol - Cell Physiol 299:C1379-C1385
    Tyan L, Sopjani M, Dërmaku-Sopjani M, Schmid E, Yang W, Xuan NT, Shumilina E, Lang F
    (See online at https://doi.org/10.1152/ajpcell.00367.2010)
  • (2010) Non-selective cation channel-mediated Ca2+-entry and activation of Ca2+/calmodulin-dependent kinase II contribute to G2/M cell cycle arrest and survival of irradiated leukemia cells. Cell Physiol Biochem 26:597-608
    Heise N, Palme D, Misovic M, Koka S, Rudner J, Lang F, Salih HR, Huber SM, Henke G
    (See online at https://doi.org/10.1159/000322327)
  • (2010) Phosphoinositide-dependent kinase PDK1 in the regulation of Ca2+ entry into mast cells. Cell Physiol Biochem 26:699-706
    Shumilina E, Zemtsova IM, Heise N, Schmid E, Eichenmüller M, Tyan L, Rexhepaj R, Lang F
    (See online at https://doi.org/10.1159/000322337)
  • (2010) Phosphoinositide-dependent kinase PDK1 in the regulation of Ca2+ entry into mast cells. Cell Physiol Biochem 26:699-706
    Shumilina E, Zemtsova IM, Heise N, Schmid E, Eichenmüller M, Tyan L, Rexhepaj R, Lang F
    (See online at https://doi.org/10.1159/000322337)
  • (2010) PI3 kinase-dependent stimulation of platelet migration by stromal cell-derived factor 1
    Kraemer BF, Borst O, Gehring EM, Schoenberger T, Urban B, Ninci E, Seizer P, Schmidt C, Bigalke B, Koch M, Martinovic I, Daub K, Merz T, Schwanitz L, Stellos K, Fiesel F, Schaller M, Lang F, Gawaz M, Lindemann S
    (See online at https://doi.org/10.1007/s00109-010-0680-8)
  • (2010) Regulation of the Ca2+ channel TRPV6 by the kinases SGK1, PKB/Akt, and PIKfyve. J Membr Biol 233:35-41
    Sopjani M, Kunert A, Czarkowski K, Klaus F, Laufer J, Föller M, Lang F
    (See online at https://doi.org/10.1007/s00232-009-9222-0)
  • (2010) Role of acidic sphingomyelinase in thymol-mediated dendritic cell death. Mol Nutr Food Res 54:1833-1841
    Xuan NT, Shumilina E, Schmid E, Bhavsar SK, Rexhepaj R, Götz F, Gulbins E, Lang F
    (See online at https://doi.org/10.1002/mnfr.200900577)
  • (2010) Role of acidic sphingomyelinase in thymol-mediated dendritic cell death. Mol Nutr Food Res 54:1833-1841
    Xuan NT, Shumilina E, Schmid E, Bhavsar SK, Rexhepaj R, Götz F, Gulbins E, Lang F
    (See online at https://doi.org/10.1002/mnfr.200900577)
  • (2010) Stimulation of electrogenic glucose transport by glycogen synthase kinase 3. Cell Physiol Biochem 26:641-646
    Rexhepaj R, Dërmaku-Sopjani M, Gehring EM, Sopjani M, Kempe DS, Föller M, Lang F
    (See online at https://doi.org/10.1159/000322331)
  • (2010) The centrosomal protein TACC3 controls paclitaxel sensitivity by modulating a premature senescence program. Oncogene 29:6184-6192
    Schmidt S, Schneider L, Essmann F, Cirstea IC, Kuck F, Kletke A, Jänicke RU, Wiek C, Hanenberg H, Ahmadian MR, Schulze-Osthoff K, Nürnberg B, Piekorz RP
    (See online at https://doi.org/10.1038/onc.2010.354)
  • (2010) The centrosome and mitotic spindle apparatus in cancer and senescence. Cell Cycle 9:4469-4473
    Schmidt S, Essmann F, Cirstea IC, Kuck F, Thakur HC, Singh M, Kletke A, Jänicke RU, Wiek C, Hanenberg H, Ahmadian MR, Schulze-Osthoff K, Nürnberg B, Piekorz RP
    (See online at https://doi.org/10.4161/cc.9.22.13684)
  • (2010) Zinc induced apoptotic death of mouse dendritic cells. Apoptosis 15:1177-1186
    Shumilina E, Xuan NT, Schmid E, Bhavsar SK, Szteyn K, Gu S, Götz F, Lang F
    (See online at https://doi.org/10.1007/s10495-010-0520-x)
  • (2010) Zinc induced apoptotic death of mouse dendritic cells. Apoptosis 15:1177-1186
    Shumilina E, Xuan NT, Schmid E, Bhavsar SK, Szteyn K, Gu S, Götz F, Lang F
    (See online at https://doi.org/10.1007/s10495-010-0520-x)
  • (2011) Ca2+/calmodulin-dependent kinase (CaMK) signaling via CaMKI and AMP-activated protein kinase contributes to the regulation of WIPI-1 at the onset of autophagy. Mol Pharmacol 80:1066-1075
    Pfisterer SG, Mauthe M, Codogno P, Proikas-Cezanne T
    (See online at https://doi.org/10.1124/mol.111.071761)
  • (2011) Deregulation of the serum-and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure. Nature Medicine 17: 1509-1513
    Salker MS, Christian M, Steel JH, Nautiya J, Lavery S, Trew G, Webster Z, Al-sabbagh M, Puchchaakayala G, Föller M, Landles C, Sharkey AM, Quenby S, Aplin JD, Reagan L, Lang F, Brosens JJ
    (See online at https://doi.org/10.1038/nm.2498)
  • (2011) Differential regulation of the pro-apoptotic multidomain protein Bak by p53 and p73 at the promoter level. Cell Death Differ 28:1130-1139
    Graupner V, Alexander E, Overkamp T, Rothfuss O, Gillissen B, Daniel PT, Schulze-Osthoff K, Essmann F
    (See online at https://doi.org/10.1038/cdd.2010.179)
  • (2011) Effect of dexamethasone on Na+/Ca2+ exchanger in dendritic cells. Am J Physiol - Cell Physiol 300:C1306-C1313
    Heise N, Shumilina E, Nurbaeva MK, Schmid E, Szteyn K, Yang W, Xuan NT, Wang K, Zemtsova IM, Duszenko M, Lang F
    (See online at https://doi.org/10.1152/ajpcell.00396.2010)
  • (2011) Effect of dexamethasone on Na+/Ca2+ exchanger in dendritic cells. Am J Physiol - Cell Physiol 300:C1306-C1313
    Heise N, Shumilina E, Nurbaeva MK, Schmid E, Szteyn K, Yang W, Xuan NT, Wang K, Zemtsova IM, Duszenko M, Lang F
    (See online at https://doi.org/10.1152/ajpcell.00396.2010)
  • (2011) Enhanced catecholamine release in mice expressing PKB/SGK-resistant GSK3. Pflugers Arch 462:811-819
    Siraskar B, Völkl J, Ahmed MS, Hierlmeier M, Gu S, Schmid E, Leibrock C, Föller M, Lang UE, Lang F
    (See online at https://doi.org/10.1007/s00424-011-1006-6)
  • (2011) Insulin-induced serine phosphorylation of IRS-2 via ERK1/2 and mTOR: studies on the function of Ser675 and Ser907. Am J Physiol – Endocrinol Metab 300:E824-E836
    Fritsche L, Neukamm S, Lehmann R, Kremmer E, Hennige AM, Hunder-Gugel A, Schenk M, Häring HU, Schleicher ED, Weigert C
    (See online at https://doi.org/10.1152/ajpendo.00409.2010)
  • (2011) Ion channels in the regulation of platelet migration. Biochem Biophys Res Commun 415:54-60
    Schmidt EM, Münzer P, Borst O, Kraemer BF, Schmid E, Urban B, Lindemann S, Ruth P, Gawaz M, Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2011.10.009)
  • (2011) Ion channels in the regulation of platelet migration. Biochem Biophys Res Commun 415:54-60
    Schmidt EM, Münzer P, Borst O, Kraemer BF, Schmid E, Urban B, Lindemann S, Ruth P, Gawaz M, Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2011.10.009)
  • (2011) Ionizing radiation induces migration of glioblastoma cells by activating BK K+ channels. Radiother Oncol 101:122-126
    Steinle M, Palme D, Misovic M, Rudner J, Dittmann K, Lukowski R, Ruth P, Huber SM
    (See online at https://doi.org/10.1016/j.radonc.2011.05.069)
  • (2011) Protein kinase C delta (PKCδ) affects proliferation of insulin-secreting cells by promoting nuclear extrusion of the cell cycle inhibitor p21Cip1/WAF1. PLoS One 6:e28828
    Ranta F, Leveringhaus J, Theilig D, Schulz-Raffelt G, Hennige AM, Hildebrand DG, Handrick R, Jendrossek V, Bosch F, Schulze-Osthoff K, Häring HU, Ullrich S
    (See online at https://doi.org/10.1371/journal.pone.0028828(2011))
  • (2011) Selection of radioresistant tumor cells and presence of ALDH1 activity in vitro. Radiother Oncol 99:300-306
    Mihatsch J, Toulany M, Bareiss PM, Grimm S, Lengerke C, Kehlbach R, Rodemann HP
    (See online at https://doi.org/10.1016/j.radonc.2011.06.003)
  • (2011) Stimulation of Ca2+-channel Orai1/STIM1 by serum- and glucocorticoid-inducible kinase 1
    Eylenstein A, Schmid EM, Heise N, Shumilina E, Schmidt S, Szteyn K, Münzer P, Nurbaeva MK, Eichenmüller M, Tyan L, Regel I, Föller M, Kuhl D, Soboloff J, Penner R, Lang F
    (See online at https://doi.org/10.1096/fj.10-178210)
  • (2011) Stimulation of Ca2+-channel Orai1/STIM1 by serum- and glucocorticoid-inducible kinase 1 (SGK1). FASEB J 25:2012-2021
    Eylenstein A, Schmid EM, Heise N, Shumilina E, Schmidt S, Szteyn K, Münzer P, Nurbaeva MK, Eichenmüller M, Tyan L, Regel I, Föller M, Kuhl D, Soboloff J, Penner R, Lang F
    (See online at https://doi.org/10.1096/fj.10-178210)
  • (2011) Stimulation of the amino acid transporter SLC6A19 by JAK2. Biochem Biophys Res Commun 414:456-461
    Bhavsar SK, Hosseinzadeh Z, Merches K, Gu S, Broer S, Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2011.09.074)
  • (2011) Stimulation of the amino acid transporter SLC6A19 by JAK2. Biochem Biophys Res Commun 414:456-461
    Bhavsar SK, Hosseinzadeh Z, Merches K, Gu S, Broer S, Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2011.09.074)
  • (2011) Stimulation of the glucose carrier SGLT1 by JAK2. Biochem Biophys Res Commun 408:(208-213
    Hosseinzadeh Z, Bhavsar SK, Shojaiefard M, Saxena A, Merches K, Sopjani M, Alesutan I and Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2011.03.036)
  • (2011) Stimulation of the glucose carrier SGLT1 by JAK2. Biochem Biophys Res Commun 408:208-213
    Hosseinzadeh Z, Bhavsar SK, Shojaiefard M, Saxena A, Merches K, Sopjani M, Alesutan I and Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2011.03.036)
  • (2011) Thymoquinone-induced platelet apoptosis. J Cell Biochem 112:3112-3121
    Towhid ST, Schmidt EM, Schmid E, Münzer P, Qadri SM, Borst O, Lang F
    (See online at https://doi.org/10.1002/jcb.23237)
  • (2011) Thymoquinone-induced platelet apoptosis. J Cell Biochem 112:3112-3121
    Towhid ST, Schmidt EM, Schmid E, Münzer P, Qadri SM, Borst O, Lang F
    (See online at https://doi.org/10.1002/jcb.23237)
  • (2011) Triggering of a novel intrinsic apoptosis pathway by the kinase inhibitor staurosporine: activation of caspase-9 in the absence of Apaf-1. FASEB J. 25:3250-3261
    Manns J, Daubrawa M, Driessen S, Paasch F, Hoffmann N, Löffler A, Lauber K, Dieterle A, Alers S, Iftner T, Schulze-Osthoff K, Stork B, Wesselborg S
    (See online at https://doi.org/10.1096/fj.10-177527)
  • (2012) A novel role for phospholipase D as an endogenous negative regulator of platelet sensitivity. Cell Signal 24:1743-1752
    Elvers M, Grenegård M, Khoshjabinzadeh H, Münzer P, Borst O, Tian H, Di Paolo G, Lang F, Gawaz M, Lindahl TL, Fälker K
    (See online at https://doi.org/10.1016/j.cellsig.2012.04.018)
  • (2012) AKT/SGK-sensitive phosphorylation of GSK3 in the regulation of L-selectin and perforin expression as well as activation induced cell death of T-lymphocytes. Biochem Biophys Res Commun 425:6-12
    Bhavsar SK, Merches K, Bobbala D, Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2012.07.030)
  • (2012) AKT/SGK-sensitive phosphorylation of GSK3 in the regulation of L-selectin and perforin expression as well as activation induced cell death of T-lymphocytes. Biochem Biophys Res Commun 425:6-12
    Bhavsar SK, Merches K, Bobbala D, Lang F
    (See online at https://doi.org/10.1016/j.bbrc.2012.07.030)
  • (2012) Chorein-sensitive polymerization of cortical actin and suicidal cell death in chorea-acanthocytosis. FASEB J 26:1526-1534
    Föller M, Hermann A, Gu S, Alesutan I, Qadri SM, Borst O, Schmidt EM, Schiele F, Müller vom Hagen J, Saft C, Schöls L, Lerche H, Stournaras C, Storch A, Lang F
    (See online at https://doi.org/10.1096/fj.11-198317)
  • (2012) Chorein-sensitive polymerization of cortical actin and suicidal cell death in chorea-acanthocytosis. FASEB J 26:1526-1534
    Föller M, Hermann A, Gu S, Alesutan I, Qadri SM, Borst O, Schmidt EM, Schiele F, Müller vom Hagen J, Saft C, Schöls L, Lerche H, Stournaras C, Storch A, Lang F
    (See online at https://doi.org/10.1096/fj.11-198317)
  • (2012) Enhanced Ca2+ entry and Na+/ Ca2+ exchanger activity in dendritic cells from AMP-activated protein kinase-deficient mice. FASEB J 26:3049-3058
    Nurbaeva MK, Schmid E, Szteyn K, Yang W, Viollet B, Shumilina E, Lang F
    (See online at https://doi.org/10.1096/fj.12-204024)
  • (2012) Enhanced Ca2+ entry and Na+/Ca2+ exchanger activity in dendritic cells from AMP-activated protein kinase-deficient mice. FASEB J 26:3049-3058
    Nurbaeva MK, Schmid E, Szteyn K, Yang W, Viollet B, Shumilina E, Lang F
    (See online at https://doi.org/10.1096/fj.12-204024)
  • (2012) Expression and functional significance of the Ca2+-activated Cl- channel ANO6 in dendritic cells. Cell Physiol Biochem 30:1319-1332
    Szteyn K, Schmid E, Nurbaeva MK, Yang W, Münzer P, Kunzelmann K, Lang F, Shumilina E
    (See online at https://doi.org/10.1159/000343321)
  • (2012) Expression and functional significance of the Ca2+-activated Cl-- channel ANO6 in dendritic cells. Cell Physiol Biochem 30:1319-1332
    Szteyn K, Schmid E, Nurbaeva MK, Yang W, Münzer P, Kunzelmann K, Lang F, Shumilina E
    (See online at https://doi.org/10.1159/000343321)
  • (2012) Funktionsanalysen zum humanen WIPI-1 Protein an autophagosomalen Membranen. Ph.D. thesis, University of Tübingen
    Pfisterer SG
  • (2012) G Protein-coupled receptor-mediated activation of p110? by G?? is required for cell transformation and invasiveness. Sci Signal 5:ra89
    Dbouk HA, Vadas O, Shymanets A, Burke JE, Salamon RS, Khalil BD, Barett MO, Waldo GL, Surve C, Hsueh C, Perisic O, Harteneck C, Shepherd PR, Harden TK, Smrcka AV, Taussig R, Bresnick AR, Nürnberg B, Williams RL, Backer JM
    (See online at https://doi.org/10.1126/scisignal.2003264)
  • (2012) G Protein-coupled receptor-mediated activation of p110? by G?? is required for cell transformation and invasiveness. Sci Signal 5:ra89
    Dbouk HA, Vadas O, Shymanets A, Burke JE, Salamon RS, Khalil BD, Barett MO, Waldo GL, Surve C, Hsueh C, Perisic O, Harteneck C, Shepherd PR, Harden TK, Smrcka AV, Taussig R, Bresnick AR, Nürnberg B, Williams RL, Backer JM
    (See online at https://doi.org/10.1126/scisignal.2003264)
  • (2012) Identification of the amino acids 300-600 of IRS-2 as 14-3-3 binding region with the importance of IFG-1/insulin-regulated phosphorylation of Ser-573. PloS One 7:e43296
    Neukamm S, Toth R, Morrice N, Campbell DG, MacKintosh C, Lehmann R, Häring HU, Schleicher ED, Weigert C
    (See online at https://doi.org/10.1371/journal.pone.0043296)
  • (2012) Intracellular cyclophilin A is an im-portant Ca²+ regulator in platelets and critically involved in arterial thrombus for-mation. Blood 120:1317-1326
    Elvers M, Herrmann A, Seizer P, Münzer P, Beck S, Schönberger T, Borst O, Martin-Romero FJ, Lang F, May AE, Gawaz M
    (See online at https://doi.org/10.1182/blood-2011-12-398438)
  • (2012) IκB(NS) protein mediates regulatory T cell development via induction of the Foxp3 transcription factor. Immunity 37:998-1008
    Schuster M, Glauben R, Plaza-Sirvent C, Schreiber L, Annemann M, Floess S, Kühl AA, Clayton LK, Sparwasser T, Schulze-Osthoff K, Pfeffer K, Huehn J, Siegmund B, Schmitz I
    (See online at https://doi.org/10.1016/j.immuni.2012.08.023)
  • (2012) Lipopolysaccharide-sensitive H+ current in dendritic cells. Am J Physiol - Cell Physiol 303:C204-C212
    Szteyn K, Yang W, Schmid E, Lang F, Shumilina E
    (See online at https://doi.org/10.1152/ajpcell.00059.2012)
  • (2012) Lipopolysaccharide-sensitive H+ current in dendritic cells. Am J Physiol - Cell Physiol 303:C204-C212
    Szteyn K, Yang W, Schmid E, Lang F, Shumilina E
    (See online at https://doi.org/10.1152/ajpcell.00059.2012)
  • (2012) Modified mRNA encoding Foxp3 protects against allergic asthma in mice through an IL-23/IL-17A-dependent mechanism. J Clin Invest 123:1216-1228
    Mays LE, Ammon-Treiber S, Mothes B, Alkhaled M, Rottenberger J, Müller-Hermelink ES, Grimm M, Mezger M, Beer-Hammer S, von Stebut-Borschitz E, Nürnberg B, Schwab M, Handgretinger R, Idzko M, Hartl D, Kormann MSD
    (See online at https://doi.org/10.1172/JCI65351)
  • (2012) Modified mRNA encoding Foxp3 protects against allergic asthma in mice through an IL-23/IL-17A-dependent mechanism. J Clin Invest 123:1216-1228
    Mays LE, Ammon-Treiber S, Mothes B, Alkhaled M, Rottenberger J, Müller-Hermelink ES, Grimm M, Mezger M, Beer-Hammer S, von Stebut-Borschitz E, Nürnberg B, Schwab M, Handgretinger R, Idzko M, Hartl D, Kormann MSD
  • (2012) Modified mRNA encoding Foxp3 protects against allergic asthma in mice through an IL-23/IL-17A-dependent mechanism. J Clin Invest 123:1216-1228
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