The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation

McKay, 2007, Integrating signals from RTKs to ERK/MAPK, Oncogene, 26, 3113, 10.1038/sj.onc.1210394 Rozengurt, 2007, Mitogenic signaling pathways induced by G protein-coupled receptors, J. Cell. Physiol., 213, 589, 10.1002/jcp.21246 Anjum, 2008, The RSK family of kinases: emerging roles in cellular signalling, Nat. Rev. Mol. Cell Biol., 9, 747, 10.1038/nrm2509 Dhillon, 2007, MAP kinase signalling pathways in cancer, Oncogene, 26, 3279, 10.1038/sj.onc.1210421 Meloche, 2007, The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition, Oncogene, 26, 3227, 10.1038/sj.onc.1210414 Sengupta, 2010, Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress, Mol. Cell, 40, 310, 10.1016/j.molcel.2010.09.026 Alessi, 2009, New insights into mTOR signaling: mTORC2 and beyond, Sci. Signal., 2, pe27, 10.1126/scisignal.267pe27 Zoncu, 2011, mTOR: from growth signal integration to cancer, diabetes and ageing, Nat. Rev. Mol. Cell Biol., 12, 21, 10.1038/nrm3025 Clerk, 2006, Peptide growth factors signal differentially through protein kinase C to extracellular signal-regulated kinases in neonatal cardiomyocytes, Cell. Signal., 18, 225, 10.1016/j.cellsig.2005.04.005 Weng, 2001, PTEN inhibits insulin-stimulated MEK/MAPK activation and cell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer model, Hum. Mol. Genet., 10, 605, 10.1093/hmg/10.6.605 Lemmon, 2010, Cell signaling by receptor tyrosine kinases, Cell, 141, 1117, 10.1016/j.cell.2010.06.011 Wohrle, 2009, Function, regulation and pathological roles of the Gab/DOS docking proteins, Cell Commun. Signal., 7, 22, 10.1186/1478-811X-7-22 Dibble, 2009, Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1, Mol. Cell. Biol., 29, 5657, 10.1128/MCB.00735-09 Julien, 2010, mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling, Mol. Cell. Biol., 30, 908, 10.1128/MCB.00601-09 Treins, 2010, Rictor is a novel target of p70 S6 kinase-1, Oncogene, 29, 1003, 10.1038/onc.2009.401 Chung, 1994, PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase, Nature, 370, 71, 10.1038/370071a0 Hutti, 2004, A rapid method for determining protein, kinase phosphorylation specificity, Nat. Methods, 1, 27, 10.1038/nmeth708 Pearce, 2010, The nuts and bolts of AGC protein kinases, Nat. Rev. Mol. Cell Biol., 11, 9, 10.1038/nrm2822 Yu, 2002, ERK negatively regulates the epidermal growth factor-mediated interaction of Gab1 and the phosphatidylinositol 3-kinase, J. Biol. Chem., 277, 19382, 10.1074/jbc.M200732200 Hoeflich, 2009, In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models, Clin. Cancer Res., 15, 4649, 10.1158/1078-0432.CCR-09-0317 Lehr, 2004, Identification of major ERK-related phosphorylation sites in Gab1, Biochemistry, 43, 12133, 10.1021/bi049753e Zhang, 2002, Receptor-specific regulation of phosphatidylinositol 3’-kinase activation by the protein tyrosine phosphatase Shp2, Mol. Cell. Biol., 22, 4062, 10.1128/MCB.22.12.4062-4072.2002 Moelling, 2002, Regulation of Raf-Akt Cross-talk, J. Biol. Chem., 277, 31099, 10.1074/jbc.M111974200 Zimmermann, 1999, Phosphorylation and regulation of Raf by Akt (protein kinase B), Science, 286, 1741, 10.1126/science.286.5445.1741 Dhillon, 2002, Regulation of Raf-1 activation and signalling by dephosphorylation, EMBO J., 21, 64, 10.1093/emboj/21.1.64 Guan, 2000, Negative regulation of the serine/threonine kinase B-Raf by Akt, J. Biol. Chem., 275, 27354, 10.1016/S0021-9258(19)61518-8 Cheung, 2008, Akt3 and mutant V600E B-Raf cooperate to promote early melanoma development, Cancer Res., 68, 3429, 10.1158/0008-5472.CAN-07-5867 Dhillon, 2002, Cyclic AMP-dependent kinase regulates Raf-1 kinase mainly by phosphorylation of serine 259, Mol. Cell. Biol., 22, 3237, 10.1128/MCB.22.10.3237-3246.2002 Dumaz, 2003, Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras, J. Biol. Chem., 278, 29819, 10.1074/jbc.C300182200 Kodaki, 1994, The activation of phosphatidylinositol 3-kinase by Ras, Curr. Biol., 4, 798, 10.1016/S0960-9822(00)00177-9 Rodriguez-Viciana, 1994, Phosphatidylinositol-3-OH kinase as a direct target of Ras, Nature, 370, 527, 10.1038/370527a0 Suire, 2002, Activation of phosphoinositide 3-kinase gamma by Ras, Curr. Biol., 12, 1068, 10.1016/S0960-9822(02)00933-8 Roux, 2004, Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase, Proc. Natl. Acad. Sci. U.S.A., 101, 13489, 10.1073/pnas.0405659101 Carriere, 2011, ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1), J. Biol. Chem., 286, 567, 10.1074/jbc.M110.159046 Foster, 2010, Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation, J. Biol. Chem., 285, 80, 10.1074/jbc.M109.029637 Herbert, 2002, The extracellular signal-regulated kinase pathway regulates the phosphorylation of 4E-BP1 at multiple sites, J. Biol. Chem., 277, 11591, 10.1074/jbc.M110367200 She, 2010, 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors, Cancer Cell., 18, 39, 10.1016/j.ccr.2010.05.023 Nada, 2009, The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes, EMBO J., 28, 477, 10.1038/emboj.2008.308 Dougherty, 2009, KSR2 is a calcineurin substrate that promotes ERK cascade activation in response to calcium signals, Mol. Cell, 34, 652, 10.1016/j.molcel.2009.06.001 Costanzo-Garvey, 2009, KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity, Cell Metab., 10, 366, 10.1016/j.cmet.2009.09.010 Yang, 2008, ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation, Nat. Cell Biol., 10, 138, 10.1038/ncb1676 Manning, 2007, AKT/PKB signaling: navigating downstream, Cell, 129, 1261, 10.1016/j.cell.2007.06.009 Biggs, 1999, Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1, Proc. Natl. Acad. Sci. U.S.A., 96, 7421, 10.1073/pnas.96.13.7421 Rena, 1999, Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B, J. Biol. Chem., 274, 17179, 10.1074/jbc.274.24.17179 Tang, 1999, Negative regulation of the forkhead transcription factor FKHR by Akt, J. Biol. Chem., 274, 16741, 10.1074/jbc.274.24.16741 Greer, 2005, FOXO transcription factors at the interface between longevity and tumor suppression, Oncogene, 24, 7410, 10.1038/sj.onc.1209086 Sears, 2000, Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability, Genes Dev., 14, 2501, 10.1101/gad.836800 Zhu, 2008, Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1, Proc. Natl. Acad. Sci. U.S.A., 105, 6584, 10.1073/pnas.0802785105 Bonni, 1999, Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms, Science, 286, 1358, 10.1126/science.286.5443.1358 Shimamura, 2000, Rsk1 mediates a MEK-MAP kinase cell survival signal, Curr. Biol., 10, 127, 10.1016/S0960-9822(00)00310-9 Tan, 1999, p90(RSK) blocks bad-mediated cell death via a protein kinase C-dependent pathway, J. Biol. Chem., 274, 34859, 10.1074/jbc.274.49.34859 Harada, 2001, p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD, Proc. Natl. Acad. Sci. U.S.A., 98, 9666, 10.1073/pnas.171301998 Harada, 1999, Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A, Mol. Cell, 3, 413, 10.1016/S1097-2765(00)80469-4 Thimmaiah, 2010, Protection from rapamycin-induced apoptosis by insulin-like growth factor-I is partially dependent on protein kinase C signaling, Cancer Res., 70, 2000, 10.1158/0008-5472.CAN-09-3693 Zha, 1996, Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L), Cell, 87, 619, 10.1016/S0092-8674(00)81382-3 She, 2005, The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells, Cancer Cell, 8, 287, 10.1016/j.ccr.2005.09.006 Qi, 2006, Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL apoptotic function, J. Biol. Chem., 281, 813, 10.1074/jbc.M505546200 Ding, 2005, Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin, Mol. Cell, 19, 159, 10.1016/j.molcel.2005.06.009 Nishikawa, 1997, Determination of the specific substrate sequence motifs of protein kinase C isozymes, J. Biol. Chem., 272, 952, 10.1074/jbc.272.2.952 Dajani, 2001, Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition, Cell, 105, 721, 10.1016/S0092-8674(01)00374-9 Shaw, 1999, Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells, FEBS Lett., 461, 120, 10.1016/S0014-5793(99)01434-9 Stambolic, 1994, Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation, Biochem. J., 303, 701, 10.1042/bj3030701 Fang, 2000, Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A, Proc. Natl. Acad. Sci. U.S.A., 97, 11960, 10.1073/pnas.220413597 Goode, 1992, Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes, J. Biol. Chem., 267, 16878, 10.1016/S0021-9258(18)41866-2 Ding, 2000, Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling, J. Biol. Chem., 275, 32475, 10.1074/jbc.M005342200 Sutherland, 1994, The alpha-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is inactivated by p70 S6 kinase or MAP kinase-activated protein kinase-1 in vitro, FEBS Lett., 338, 37, 10.1016/0014-5793(94)80112-6 Sutherland, 2005, Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells, Oncogene, 24, 4281, 10.1038/sj.onc.1208590 Stratford, 2008, Y-box binding protein-1 serine 102 is a downstream target of p90 ribosomal S6 kinase in basal-like breast cancer cells, Breast Cancer Res., 10, R99, 10.1186/bcr2202 Evdokimova, 2006, Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species, Mol. Cell. Biol., 26, 277, 10.1128/MCB.26.1.277-292.2006 Yamnik, 2010, mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor alpha serine 167 phosphorylation, FEBS Lett., 584, 124, 10.1016/j.febslet.2009.11.041 Sun, 2001, Phosphatidylinositol-3-OH kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K, Cancer Res., 61, 5985 Joel, 1998, pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167, Mol. Cell. Biol., 18, 1978, 10.1128/MCB.18.4.1978 Besson, 2004, p27Kip1 modulates cell migration through the regulation of RhoA activation, Genes Dev., 18, 862, 10.1101/gad.1185504 Larrea, 2009, RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility, Proc. Natl. Acad. Sci. U.S.A., 106, 9268, 10.1073/pnas.0805057106 Fujita, 2002, Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization, J. Biol. Chem., 277, 28706, 10.1074/jbc.M203668200 Fujita, 2003, Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization, J. Biol. Chem., 278, 49254, 10.1074/jbc.M306614200 Hong, 2008, mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation, Mol. Cell, 30, 701, 10.1016/j.molcel.2008.04.027 Shin, 2005, Phosphorylation of p27Kip1 at Thr-157 interferes with its association with importin alpha during G1 and prevents nuclear re-entry, J. Biol. Chem., 280, 6055, 10.1074/jbc.M412367200 Woo, 2004, Ribosomal S6 kinase (RSK) regulates phosphorylation of filamin A on an important regulatory site, Mol. Cell. Biol., 24, 3025, 10.1128/MCB.24.7.3025-3035.2004 Vadlamudi, 2002, Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1, Nat. Cell Biol., 4, 681, 10.1038/ncb838 Ravid, 2008, Filamin A is a novel caveolin-1-dependent target in IGF-I-stimulated cancer cell migration, Exp. Cell Res., 314, 2762, 10.1016/j.yexcr.2008.06.004 Chou, 1996, The 70 kDa S6 kinase complexes with and is activated by the Rho family G proteins Cdc42 and Rac1, Cell, 85, 573, 10.1016/S0092-8674(00)81257-X Whale, 2011, Signalling to cancer cell invasion through PAK family kinases, Front. Biosci., 16, 849, 10.2741/3724 Holz, 2005, mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events, Cell, 123, 569, 10.1016/j.cell.2005.10.024 van Gorp, 2009, AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B, Oncogene, 28, 95, 10.1038/onc.2008.367 Roux, 2007, RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation, J. Biol. Chem., 282, 14056, 10.1074/jbc.M700906200 Ruvinsky, 2006, Ribosomal protein S6 phosphorylation: from protein synthesis to cell size, Trends Biochem. Sci., 31, 342, 10.1016/j.tibs.2006.04.003 Abe, 2009, p90 ribosomal S6 kinase and p70 ribosomal S6 kinase link phosphorylation of the eukaryotic chaperonin containing TCP-1 to growth factor, insulin, and nutrient signaling, J. Biol. Chem., 284, 14939, 10.1074/jbc.M900097200 Yoon, 2008, Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport, Mol. Cell, 29, 362, 10.1016/j.molcel.2007.12.024 Geraghty, 2007, Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF PMA and AICAR, Biochem. J., 407, 231, 10.1042/BJ20070649 Kane, 2002, A method to identify serine kinase substrates Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain, J. Biol. Chem., 277, 22115, 10.1074/jbc.C200198200 Di Nicolantonio, 2010, Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus, J. Clin. Invest., 120, 2858, 10.1172/JCI37539 Flaherty, 2010, Inhibition of mutated, activated BRAF in metastatic melanoma, N. Engl. J. Med., 363, 809, 10.1056/NEJMoa1002011 Villanueva, 2010, Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K, Cancer Cell, 18, 683, 10.1016/j.ccr.2010.11.023 Johannessen, 2010, COT drives resistance to RAF inhibition through MAP kinase pathway reactivation, Nature, 468, 968, 10.1038/nature09627 Nazarian, 2010, Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation, Nature, 468, 973, 10.1038/nature09626 Kinkade, 2008, Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model, J. Clin. Invest., 118, 3051 Engelman, 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers, Nat. Med., 14, 1351, 10.1038/nm.1890 Mirzoeva, 2009, Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition, Cancer Res., 69, 565, 10.1158/0008-5472.CAN-08-3389 Carracedo, 2008, Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer, J. Clin. Invest., 118, 3065