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PKCδ and mTOR interact to regulate stress and IGF-I induced IRS-1 Ser312 phosphorylation in breast cancer cells

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Summary

IRS-1 (Insulin Receptor Substrate-1) is an adaptor protein important for insulin and IGF-I receptor (Insulin-like Growth Factor-IR) transduction to downstream targets. One mechanism recently identified to downregulate IGF-I or insulin receptor signaling in diabetic models is IRS-1 Ser312 phosphorylation. To date, the importance of this residue in cancer is unknown. This paper identifies mechanisms leading to Ser312 regulation in MCF-7 breast cancer cells. Whereas IGF-I phosphorylation of IRS312 is PI (phosphatidylinositol) 3-kinase dependent, anisomycin stress treatment requires JNK activation to induce phosphorylation of IRS312. We show that both IGF-I and anisomycin stress treatment converge downstream onto mTOR (Mammalian Target of Rapamycin) and PKCδ (Protein Kinase C-delta) to induce IRS-1 Ser312 phosphorylation. mTOR associates with IRS-1 and is primarily required for Ser312 phosphorylation in response to stress or IGF-I treatment. PKCδ binds to mTOR and its activity is also important for stress or IGF-I mediated Ser312 phosphorylation. Thus, mTOR and PKCδ convey diverse signals to regulate IRS-1 function.

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References

  1. D Yee (2002) ArticleTitleThe insulin-like growth factor system as a target in breast cancer Semin Oncol 29 86–95 Occurrence Handle10.1053/sonc.2002.34060 Occurrence Handle1:CAS:528:DC%2BD38XmsFWnt78%3D Occurrence Handle12138402

    Article  CAS  PubMed  Google Scholar 

  2. DR Alessi M Andejelkovic B Caudwell P Cron N Morrice P Cohen BA Hemmings (1996) ArticleTitleInsulin and IGF-I EMBO J 15 6541–6551 Occurrence Handle1:CAS:528:DyaK2sXht1Oqs7o%3D Occurrence Handle8978681

    CAS  PubMed  Google Scholar 

  3. B Vanhaesebroack DR Alessi (2000) ArticleTitleThe PI3K-PDK1 connection: more than just a road to PKB Biochem J 346 561–576 Occurrence Handle10.1042/0264-6021:3460561 Occurrence Handle1:CAS:528:DC%2BD3cXit1Kku78%3D Occurrence Handle10698680

    Article  CAS  PubMed  Google Scholar 

  4. JP Peyrat J Bonneterre H Jammes R Beuscart B Hecquet J Djiane J Lefebvre A Demaille (1990) ArticleTitleInsulin-like growth factor 1 receptors (IGF1-R) and IGF1 in human breast tumors J Steroid Biochem and Mol Biol 37 823–827 Occurrence Handle10.1016/0960-0760(90)90426-L Occurrence Handle1:CAS:528:DyaK3MXhtF2msrw%3D

    Article  CAS  Google Scholar 

  5. JS Oh JE Kucab PR Bushel K Martin L Bennett J Collins RP DiAugustine JC Barrett CA Afshari SE Dunn (2004) ArticleTitleExpression of the insulin-like growth factor I receptor and urokinase plasminogen activator in breast cancer is associated with poor survival: potential for intervention with 17-allylamino geldanamycin Cancer Research 64 286–291 Occurrence Handle14729636

    PubMed  Google Scholar 

  6. Y-H Tseng K Ueki KM Kriaucianas CR Kahn (2002) ArticleTitleDifferential roles of insulin receptor substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin J of Bio Chem 277 31601–31611 Occurrence Handle10.1074/jbc.M202932200 Occurrence Handle1:CAS:528:DC%2BD38XmslOqtrs%3D

    Article  CAS  Google Scholar 

  7. AV Lee JL Gooch S Oesterrich RL Guler D Yee (2000) ArticleTitleInsulin-like growth factor-I-induced degradation of insulin receptor substrate 1 is mediated by the 26S proteasome and blocked by phosphatidylinositol 3′-kinase inhibition Mol Cell Biol 20 1489–1496 Occurrence Handle10.1128/MCB.20.5.1489-1496.2000 Occurrence Handle1:CAS:528:DC%2BD3cXhtF2nsbg%3D Occurrence Handle10669726

    Article  CAS  PubMed  Google Scholar 

  8. T Haruta T Uno J Kawahara A Takano K Egawa PM Sharma JM Olefsk M Kobayashi (2000) ArticleTitleA rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1 Mol Endocrinol 14 783–794 Occurrence Handle10.1210/me.14.6.783 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Wgtr8%3D Occurrence Handle10847581

    Article  CAS  PubMed  Google Scholar 

  9. D Hartley GM Cooper (2002) ArticleTitleRole of mTOR in the degradation of IRS-1: regulation of PP2A activity J Cell Biochem 85 304–314 Occurrence Handle10.1002/jcb.10135 Occurrence Handle1:CAS:528:DC%2BD38XivVyqsrg%3D Occurrence Handle11948686

    Article  CAS  PubMed  Google Scholar 

  10. K Paz R Hemi D LeRoith A Karasik E Elhanany H Kanety Y Zick (1997) ArticleTitleA molucular basis for insulin resistance J Biol Chem 272 29911–29918 Occurrence Handle10.1074/jbc.272.47.29911 Occurrence Handle1:CAS:528:DyaK2sXnsFWnsbY%3D Occurrence Handle9368067

    Article  CAS  PubMed  Google Scholar 

  11. K Paz H Voliovitch YR Hadari CT Roberts D LeRoith Y Zick (1996) ArticleTitleInteraction between the insulin receptor and its downstream effectors J Biol Chem 271 6998–7003 Occurrence Handle10.1074/jbc.271.25.15084 Occurrence Handle1:CAS:528:DyaK28XhvVyit7s%3D Occurrence Handle8636129

    Article  CAS  PubMed  Google Scholar 

  12. ME Hartman M Villela-Bach J Chen GG Freund (2001) ArticleTitleFrap-dependent serine phosphorylation of IRS-1 inhibits IRS-1 tyrosine phosphorylation Biochem Biophys Res Commun 280 776–781 Occurrence Handle10.1006/bbrc.2000.4214 Occurrence Handle1:CAS:528:DC%2BD3MXls1aktA%3D%3D Occurrence Handle11162588

    Article  CAS  PubMed  Google Scholar 

  13. V Aguirre ED Werner J Giraud YH Lee SE Schoelson MF White (2002) ArticleTitlePhosporylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action J Biol Chemi 277 1531–1537 Occurrence Handle10.1074/jbc.M101521200 Occurrence Handle1:CAS:528:DC%2BD38XnvFyjtQ%3D%3D

    Article  CAS  Google Scholar 

  14. BJ Goldstein A Bittner-Kowalczyk MF White M Harbeck (2000) ArticleTitleTyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein J Biol Chem 276 4283–4289 Occurrence Handle10.1074/jbc.275.6.4283

    Article  Google Scholar 

  15. BT Solow S Harada BJ Goldstein JA Smith MF White L Jarett (1999) ArticleTitleDifferential modulation of the tyrosine phosphorylation state of the insulin receptor by IRS (insulin receptor subunit) proteins Mol Endocrinol 13 1784–1798 Occurrence Handle10.1210/me.13.10.1784 Occurrence Handle1:CAS:528:DyaK1MXms1Omt70%3D Occurrence Handle10517679

    Article  CAS  PubMed  Google Scholar 

  16. K Paz Y.-F Liu H Shorer R Hemi D LeRoith M Quan H Kanety R Seger Y Zick (1999) ArticleTitlePhosphorylation of insulin receptor substrate-1 (IRS-1) by protein kinase B positively regulates IRS-1 function J Biol Chem 274 28816–28822 Occurrence Handle10.1074/jbc.274.40.28816 Occurrence Handle1:CAS:528:DyaK1MXmsFWnsLc%3D Occurrence Handle10497255

    Article  CAS  PubMed  Google Scholar 

  17. V Aguirre T Ucida L Yenush R Davis MF White (2000) ArticleTitleThe c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor-1 and phosphorylation of ser307 J␣Biol Chem 275 9047–9054 Occurrence Handle10.1074/jbc.275.12.9047 Occurrence Handle1:CAS:528:DC%2BD3cXit1emt7Y%3D Occurrence Handle10722755

    Article  CAS  PubMed  Google Scholar 

  18. YH Lee J Giraud RJ Davis MF White (2003) ArticleTitlec-Jun N-terminal Kinase (JNK) Mediates Feedback Inhibition of the insulin signaling Cascade J Biol Chem 278 2896–2902 Occurrence Handle10.1074/jbc.M208359200 Occurrence Handle1:CAS:528:DC%2BD3sXmt1Gnuw%3D%3D Occurrence Handle12417588

    Article  CAS  PubMed  Google Scholar 

  19. CL Mamay AM Mingo-Sion DM Wolf MD Molina CL VanDen Berg (2003) ArticleTitleAn inhibitory function for JNK in the regulation of IGF-I signaling in breast cancer Oncogene 22 602–614 Occurrence Handle10.1038/sj.onc.1206186 Occurrence Handle1:CAS:528:DC%2BD3sXmslGksQ%3D%3D Occurrence Handle12555073

    Article  CAS  PubMed  Google Scholar 

  20. MW Greene H Sakaue L Wang DR Alessi RA Roth (2003) ArticleTitleModulation of insulin-stimulated degradation of human insulin receptor substrate-1 by serine 312 phosphorylation J Biol Chem 278 8199–8211 Occurrence Handle10.1074/jbc.M209153200 Occurrence Handle1:CAS:528:DC%2BD3sXhsF2hsrs%3D Occurrence Handle12510059

    Article  CAS  PubMed  Google Scholar 

  21. K De Fea RA Roth (1997) ArticleTitleModulation of insulin receptor substrate-1 tyrosine phosphorylation and function by mitogen-activated protein kinase J Biol Chem 272 31400–31406 Occurrence Handle10.1074/jbc.272.50.31400 Occurrence Handle1:CAS:528:DyaK2sXotVSks7g%3D Occurrence Handle9395471

    Article  CAS  PubMed  Google Scholar 

  22. MW Greene N Morrice RS Garofalo RA Roth (2004) ArticleTitleModulation of human insulin receptor substrate-1 phosphorylation by protein kinase Cδ Biochem J 378 105–116 Occurrence Handle1:CAS:528:DC%2BD2cXitlSnsr8%3D Occurrence Handle14583092

    CAS  PubMed  Google Scholar 

  23. Z Gao D Hwang F Bataille M Lefevre D York MJ Quon J Ye (2002) ArticleTitleSerine Phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex J Biol Chem 277 48115–48121 Occurrence Handle1:CAS:528:DC%2BD38Xptlegsr4%3D Occurrence Handle12351658

    CAS  PubMed  Google Scholar 

  24. L Rui V Aguirre JK Kim GI Shulman A Lee A Corbould A Dunaif MF White (2001) ArticleTitleInsulin/IGF-1 and TNF-α stimulates phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways J Clin Invest 107 181–189 Occurrence Handle1:CAS:528:DC%2BD3MXkvVChsA%3D%3D Occurrence Handle11160134

    CAS  PubMed  Google Scholar 

  25. PH Scott GJ Brunn AD Kohn RA Roth JC Lawrence (1998) ArticleTitleEvidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by protein kinase B signaling pathway Proceedings of the National Academy of Science of the United States of America 95 7772–7777 Occurrence Handle1:CAS:528:DyaK1cXktFCgsLs%3D

    CAS  Google Scholar 

  26. A Sekulic CC Hudson JL Homme P Yin DM Otterness LM Karnitz RT Abraham (2000) ArticleTitleA direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells Cancer Res 60 3504–3513 Occurrence Handle1:CAS:528:DC%2BD3cXkvFChsL0%3D Occurrence Handle10910062

    CAS  PubMed  Google Scholar 

  27. PE Burnett RK Barrow NA Cohen SH Snyder DM Sabatini (1998) ArticleTitleRAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 Proc Nat Acad Sci 95 1432–1437 Occurrence Handle1:CAS:528:DyaK1cXht1Wqsbo%3D Occurrence Handle9465032

    CAS  PubMed  Google Scholar 

  28. LP McMahon KM Choi T-A Lin RT Abraham JC Lawrence (2002) ArticleTitleThe rapamycin-binding domain governs substrate selectivity by the mammalian target of rapamycin Mol Cell Biol 22 7428–7437 Occurrence Handle1:CAS:528:DC%2BD38XotVKhs7c%3D Occurrence Handle12370290

    CAS  PubMed  Google Scholar 

  29. D Parekh W Ziegler K Yonezawa K Hara PJ Parker (1999) ArticleTitleMammalian TOR controls one of two kinase pathways acting upon nPKCδ and nPKCɛ J Biol Chem 274 34758–34763 Occurrence Handle1:CAS:528:DyaK1MXnvFyrsLo%3D Occurrence Handle10574945

    CAS  PubMed  Google Scholar 

  30. J Srivastava J Goris SM Dilworth PJ Parker (2002) ArticleTitleDephosphorylation of PKCδ by protein phosphatase 2Ac and its inhibition by nucleotides FEBS Lett 516 265–269 Occurrence Handle1:CAS:528:DC%2BD38XivVaiur4%3D Occurrence Handle11959144

    CAS  PubMed  Google Scholar 

  31. JA Le Good W Ziegler D Parekh DR Alessi P Cohen PJ Parker (1998) ArticleTitleProtein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1 Science 281 2042–2045 Occurrence Handle1:CAS:528:DyaK1cXmtlKlsbg%3D Occurrence Handle9748166

    CAS  PubMed  Google Scholar 

  32. V Kumar P Pandey D Sabatini M Kumar PK Majumder A Bharti G Carmichael D Kufe S Kharbanda (2000) ArticleTitleFunctional interaction between RAFT1/FARP/mTOR and protein kinase Cδ in the regulation of cap-dependent initiation of translation EMBO J 19 1087–1097 Occurrence Handle1:CAS:528:DC%2BD3cXitVyrs7k%3D Occurrence Handle10698949

    CAS  PubMed  Google Scholar 

  33. del Rincon, SV, Guo, Q, Morelli, C, Shiu, H-Y, Surmacz, E, and Miller, WH Retinoic acid mediates degradation of IRS-1 by the ubiquitin-proteosome pathway, via a PKC-dependent mechanism. Oncogene, 1–11. 2004

  34. O Potapova M Gorospe F Bost NM Dean WA Gaarde D Mercola NJ Holbrook (2000) ArticleTitlec-Jun N-terminal kinase is for growth of human T98G glioblastoma cells J Biol Chem 275 24767–24775 Occurrence Handle1:CAS:528:DC%2BD3cXlsl2jtrg%3D Occurrence Handle10825181

    CAS  PubMed  Google Scholar 

  35. TF Franke S-I Yang TO Chan K Datta A Kaziauskas DK Morrison DR Kaplan PN Tsichlis (1995) ArticleTitleThe protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase Cell 81 727–736 Occurrence Handle1:CAS:528:DyaK2MXmtFOiur8%3D Occurrence Handle7774014

    CAS  PubMed  Google Scholar 

  36. M Hibi A Lin T Smeal A Minden M Karin (1993) ArticleTitleIdentification of an oncoprotein- and UV-responsive protein kinase that bind and potentiate the c-Jun activation domain Genes Dev 7 2135–2148 Occurrence Handle1:CAS:528:DyaK2cXisVyksQ%3D%3D Occurrence Handle8224842

    CAS  PubMed  Google Scholar 

  37. BL Bennett DT Sasaki BW Murray EC O’Leary ST Sakata W Xu JC Leisten A Motiwala S Pierce Y Satoh SS Bhagwat AM Manning DW Anderson (2001) ArticleTitleSP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase Proc Nat Acad Sci USA 98 13681–13686 Occurrence Handle1:CAS:528:DC%2BD3MXovVynsbg%3D Occurrence Handle11717429

    CAS  PubMed  Google Scholar 

  38. M Barlund F Forozan J Kononen (2000) ArticleTitleDetecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis J Nat Cancer Inst 92 1252–1259 Occurrence Handle1:CAS:528:DC%2BD3cXlvFyhsb0%3D Occurrence Handle10922410

    CAS  PubMed  Google Scholar 

  39. VI Shifrin P Anderson (1999) ArticleTitleTrichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis J Biol Chem 274 13985–13992 Occurrence Handle1:CAS:528:DyaK1MXjsFWqsrw%3D Occurrence Handle10318810

    CAS  PubMed  Google Scholar 

  40. H-Y Lee H Srinivas D Xia Y Lu R Superty R LaPushin C Gomez-Manzano AM Gal GL Walsh T Force K Ueki GB Mills JM Kurie (2003) ArticleTitleEvidence that phosphatidylinositol 3-kinase- and mitogen-activated protein kinase kinase-4/c-Jun NH2-terminal kinase-dependent pathways cooperate to maintain lung cancer cell survival J Biol Chem 278 23630–23638 Occurrence Handle1:CAS:528:DC%2BD3sXkslygt70%3D Occurrence Handle12714585

    CAS  PubMed  Google Scholar 

  41. SA Molton DE Todd SJ Cook (2003) ArticleTitleSelective activation of c-Jun N-terminal kinase (JNK) pathway fails to elicit Bax activation or apoptosis unless the phosphoinositide 3′-kinase (PI3K) pathway is inhibited Oncogene 22 4690–4701 Occurrence Handle1:CAS:528:DC%2BD3sXls1Gjtb8%3D Occurrence Handle12879014

    CAS  PubMed  Google Scholar 

  42. C Brodie PM Blumberg (2003) ArticleTitleRegulation of cell apoptosis by protein kinase c δ Apoptosis 8 19–27 Occurrence Handle1:CAS:528:DC%2BD38XpsFyjurY%3D Occurrence Handle12510148

    CAS  PubMed  Google Scholar 

  43. V Kumar D Sabatini P Pandey A-C Gingras PK Majumder M Kumar Z-M Yuan G Carmichael R Weichselbaum N Sonenberg D Kufe S Kharbanda (2000) ArticleTitleRegulation of the rapamycin and FKBP-target 1/mammalian target of rapamcyin and cap-dependent initiation of translation by the c-Abl protein tyrosine kinase J Biol Chem 275 10779–10787 Occurrence Handle1:CAS:528:DC%2BD3cXislShsrY%3D Occurrence Handle10753870

    CAS  PubMed  Google Scholar 

  44. SC Kiley KJ Clark SK Duddy DR Welch S Jaken (1999) ArticleTitleIncreased protein kinase Cδ in mammary tumor cells: relationship to transformation and metastatic progression Oncogene 18 6748–6757 Occurrence Handle10.1038/sj.onc.1203101 Occurrence Handle1:CAS:528:DyaK1MXotV2lsr8%3D Occurrence Handle10597283

    Article  CAS  PubMed  Google Scholar 

  45. SC Kiley KJ Clark M Goodnough DR Welch S Jaken (1999) ArticleTitleProtein Kinase C δ involvement in mammary tumor cell metastasis Cancer Res 59 3230–3238 Occurrence Handle1:CAS:528:DyaK1MXksVGjsrk%3D Occurrence Handle10397270

    CAS  PubMed  Google Scholar 

  46. H Kaneto Y Nakatani T Miyatsuka D Kawamori T Matsuoka M Matsuhisa Y Kajimoto H Ichiijo M Hori (2004) ArticleTitlePossible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide Nat Med 10 1128–1132 Occurrence Handle1:CAS:528:DC%2BD2cXnvFyntbg%3D Occurrence Handle15448687

    CAS  PubMed  Google Scholar 

  47. J Hirosumi G Tuncman L Chang CZ Gorgun KT Uysal K Maeda M Karin GS Hotamisligil (2002) ArticleTitleA central role for JNK in obesity and insulin resistance Nature(London) 420 333–336 Occurrence Handle1:CAS:528:DC%2BD38XovVekt7g%3D

    CAS  Google Scholar 

  48. A Jaeschke MP Czech RJ Davis (2004) ArticleTitleAn essential role of the JIP1 scaffold protein for JNK activation in adipose tissue Genes Dev 18 1976–1980 Occurrence Handle1:CAS:528:DC%2BD2cXmvFKqsb0%3D Occurrence Handle15314024

    CAS  PubMed  Google Scholar 

  49. ED Werner J Lee L Hansen M Yuan SE Shoelson (2004) ArticleTitleInsulin resistance due to phosphorylation of Insulin Receptor Substrate-1 at serine 302 J Biol Chem 279 35298–35305 Occurrence Handle1:CAS:528:DC%2BD2cXmsl2iurk%3D Occurrence Handle15199052

    CAS  PubMed  Google Scholar 

  50. LS Harrington GM Findlay A Gray T Tolkacheva S Wigfield H Rebholz J Barnett NR Leslie S Cheng PR Shepherd I Gout P Downes RF Lamb (2004) ArticleTitleThe TSC1–2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins J Cell Biol 166 213–223 Occurrence Handle1:CAS:528:DC%2BD2cXlvFKqsrw%3D Occurrence Handle15249583

    CAS  PubMed  Google Scholar 

  51. CJ Carlson MF White CM Rondinone (2004) ArticleTitleMammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation Biochem Biophys Res Commun 316 533–539 Occurrence Handle1:CAS:528:DC%2BD2cXitFKhu7o%3D Occurrence Handle15020250

    CAS  PubMed  Google Scholar 

  52. SE Dunn RA Hardman FW Kari JC Barrett (1997) ArticleTitleInsulin-like growth factor-1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced diverse anticancer drugs Cancer Res 57 2687–2693 Occurrence Handle1:CAS:528:DyaK2sXktlSis7s%3D Occurrence Handle9205078

    CAS  PubMed  Google Scholar 

  53. JL Gooch CL VanDen Berg D Yee (1999) ArticleTitleInsulin-like growth factor (IGF)-I rescues breast cancer cells from chemotherapy-induced cell death- proliferative and anti-apoptotic effects Breast Cancer Res Treat 56 1–10 Occurrence Handle1:CAS:528:DyaK1MXmvVyns7s%3D Occurrence Handle10517338

    CAS  PubMed  Google Scholar 

  54. S Huang PJ Houghton (2003) ArticleTitleTargeting mTOR signaling for cancer therapy Current Opinions in Pharmacol 3 1–7

    Google Scholar 

  55. M Hidalgo EK Rowinsky (2000) ArticleTitleThe rapamycin-sensitive signal transduction pathway as a target for cancer therapy Oncogene 19 6680–6686 Occurrence Handle1:CAS:528:DC%2BD3MXhsF2rs7w%3D Occurrence Handle11426655

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. School of Pharmacy,School of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, C238, Denver, CO, 80272, USA

    Amy M. Mingo-Sion, Heather A. Ferguson & Carla L. Van Den Berg

  2. Departments of Basic Science and Oral Research, School of Dentistry, and Structural Biology, School of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA

    Mary E. Reyland

  3. Isis Pharmaceuticals Inc, Carlsbad, CA, USA

    Erich Koller

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  1. Amy M. Mingo-Sion
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  2. Heather A. Ferguson
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  3. Erich Koller
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  4. Mary E. Reyland
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  5. Carla L. Van Den Berg
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Correspondence to Carla L. Van Den Berg.

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Mingo-Sion, A.M., Ferguson, H.A., Koller, E. et al. PKCδ and mTOR interact to regulate stress and IGF-I induced IRS-1 Ser312 phosphorylation in breast cancer cells. Breast Cancer Res Treat 91, 259–269 (2005). https://doi.org/10.1007/s10549-005-0669-0

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