publications
Mitogenic/Oncogenic Signaling via the ERK-MAP kinase/RSK pathway
Chen R-H, Sarnecki C, and Blenis J. Nuclear localization and regulation of the erk- and rsk-encoded protein kinases. Mol. Cell. Biol. 1992; 12:915-927.
Wood K, Sarnecki C, Roberts TM and Blenis J. c-Ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1 and RSK. Cell 1992; 68: 1041-1050.
Chen R-H and Blenis J. Phosphorylation of the c-Fos transrepression domain by MAP kinase and RSK. Proc. Natl. Acad. Sci. USA 1993; 90: 10952-10956.
Fisher T L and Blenis J. Evidence for two catalytically active kinase domains in pp90rsk. Mol. Cell. Biol., 1996; 16: 1212-1219.
Chen R-H, Juo P, Curran T and Blenis J. MAP kinase and RSK facilitate transformation induced by c-Fos. Oncogene, 1996; 12: 1493-1502.
Nakajima T, Fukamizu A, Takahashi J, Gage FH, Fisher T, Blenis J and Montminy MR The signal-dependent coactivator CBP is a nuclear target for pp90Rsk. Cell 1996; 86:465-474.
Grammer TC and Blenis J. Evidence for MEK-independent pathways regulating the prolonged activation of the ERK-MAP kinases. Oncogene 1997; 14: 1635-1642. (PDF)
Chung J, Uchida E, Grammer TC and Blenis J. STAT3 serine phosphorylation by ERK-dependent and -independent pathways negatively modulates its tyrosine phosphorylation. Mol. Cell. Biol. 1997; 17: 6508-6516.
Richards SA, Fu J, Romanelli A, Shimamura A and Blenis J. Ribosomal S6 kinase 1 (RSK1) activation requires signals dependent on and independent of the MAP kinase ERK. Current Biology 1999; 9: 810-820. (PDF)
Richards SA, Dreisbach VC, Murphy LO and Blenis J. Characterization of regulatory events associated with membrane targeting of p90 ribosomal S6 kinase 1. Mol. Cell. Biol. 2001; 21: 7470-7480. (PDF)
Murphy LO, Smith S, Chen R-H, Fingar DC and Blenis J. Molecular interpretation of ERK signal duration by immediate early gene products. Nat.Cell Biol. 2002; 4: 556-564. (PDF) (see commentaries - NCB, JCB)
Roux PP, Richards SA and Blenis J. Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates ERK docking and RSK activity. Mol. Cell. Biol. 2003; 23: 4796-4804. (PDF)
Murphy LO, MacKeigan JP and Blenis J. A network of immediate early gene products propagates subtle differences in mitogen-activated protein kinase signal amplitude and duration. Mol. Cell Biol. 2004. 24: 144-153. (PDF)
Woo MS, Ohta Y, Rabinovitz I, Stossel TP and Blenis J. Ribosomal S6 Kinase (RSK) regulates phosphorylation of Filamin A on an important regulatory site. Mol. Cell Biol. 2004; 24: 3025-3035. (PDF)
Roux P, Ballif BA, Anjum R, Gygi SP and Blenis J. Tumor promoting phorbol esters and activated ras inactivate the tuberous sclerosis tumor promoter complex via RSK. Proc. Natl. Acad. Sci. USA 2004; 101:13489-13494 . (PDF)
Ballif BA, Roux P, Gerber S.A., MacKeigan JP, Blenis J and Gygi, S.A. Quantitative Phosphorylation Profining of the ERK-RSK Signaling Cassette and its Target, the Tuberous Sclerosis Tumor Suppressor Complex. Proc. Natl. Acad. Sci. USA 2005; 102: 667-672. (PDF)
MacKeigan JP*, Murphy LO*, Dimitri CA, and Blenis J. Graded MAPK activity precedes switch-like c-Fos induction in mammalian cells. Mol. Cell Biol. 2005; 25: 4676–4682. (PDF)
Christopher A. Dimitri*, William Dowdle, Jeffrey P. MacKeigan, John Blenis 1 , Leon O. Murphy*. Spatially separate docking sites on ERK2 regulate distinct signalling events in vivo. Current Biology 2005; 15: 1319-1324. (PDF)
Mitogenic/Oncogenic Signaling via the p70-S6 protein kinase pathway
Chung J, Kuo C, Crabtree GR and Blenis J. Rapamycin: FKBP specifically blocks growth-dependent activation of and signaling by the 70kD-S6 protein kinases. Cell 1992; 69:1227-1236.
Kuo CJ, Chung J, Fiorentino DF, Flanagan WM, Blenis J and Crabtree GR. Rapamycin specifically inhibits IL-2-induced activation of p70-S6 kinase. Nature 1992; 358:70-73.
Chung J, Grammer T, Lemon K, Kazlauskas A, and Blenis J. PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature 1994; 370: 71-75.
Cheatham L, Monfar M, Chou MM and Blenis J. Structural and functional analysis of p70 S6 kinase. Proc. Natl. Acad. Sci. USA, 1995; 92: 11696-11700.
Chou MM and Blenis J. The 70kD S6 kinase complexes with and is activated by the Rho family G proteins Cdc42 and Rac1. Cell, 1996; 85: 573-583.
Grammer TC and Blenis J. The serine protease inhibitors, tosylphenylalanine chloromethyl ketone and tosyllysine chloromethyl ketone, potently inhibit pp70S6k activation. J. Biol. Chem. 1996; 271: 23650-23652.
Romanelli A, Martin KA, Toker A and Blenis J. P70 S6 kinase is regulated by atypical protein kinase Cz and participates in a PI3-K-regulated signaling complex. Mol. Cell. Biol. 1999; 19: 2921-2928.
Lee-Fruman KK, Kuo CJ, Lippincott J, Terada N and Blenis J. Characterization of S6K2, a novel kinase homologous to S6K1. Oncogene 1999; 18: 5108-5114.
Martin KA, Schalm SS, Richardson C, Romanelli A, Keon KL and Blenis J. Regulation of S6K2 by effectors of the PI3-kinase pathway. J Biol Chem. 2001; 276: 7884-7891. (PDF)
Martin KA, Schalm SS, Romanelli A, Keon KL and Blenis J. S6K2 inhibition by a potent C-terminal repressor domain is relieved by MEK-regulated phosphorylation. J Biol Chem. 2001; 276: 7892-7898. (PDF)
Ballif BA, Shimamura A, Pae E and Blenis J. Disruption of 3-Phosphoinositide-Dependent Kinase 1 (PDK1) Signaling by the anti-tumorigenic and anti-proliferative agent N-?-tosyl-L-phenylalanyl chloromethyl ketone. J Biol Chem. 2001; 276: 12466-12475. (PDF)
Schalm S and Blenis J. Identification of a conserved motif required for mTOR signaling. Current Biol. 2002; 12: 632-639. (PDF)
Fingar DC, Salama S, Tsou C, Harlow E, Blenis J. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 2002;16:1472-1487. (PDF)
Manning BD, Tee AR, Logsdon MN, Blenis J and Cantley LC. Identification of the TSC-2 tumor suppressor gene product tuberin as a target of the PI3 kinase/Akt pathway. Mol. Cell 2002; 10: 151-162. (PDF)
Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC and Blenis J. Tuberous Sclerosis Complex-1 and –2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc. Natl. Acad. Sci. USA 2002; 99: 13571-13576. (PDF)
Romanelli A, Dreisbach V and Blenis J. Characterization of phosphatidylinositol 3-kinase-dependent phosphorylation of the hydrophobic motif site Thr389 in p70 S6 kinase 1. J Biol Chem. 2002; 277: 40281-40289. (PDF)
Schalm S, Fingar DC, Sabatini DM and Blenis J. TOS motif-mediated raptor binding regulates 4E-BP1 multi-site phosphorylation and function. Current Biology 2003; 13: 797-806. (PDF)
Tee AR, Manning BD, Roux P, Cantley LC and Blenis J. The Tuberous Sclerosis Complex gene products, tuberin and hamartin, control mTOR signaling by acting as a GTPase-activating protein complex towards Rheb. Current Biology 2003; 13: 1259-1268. (PDF)
Tee AR, Anjum R and Blenis J. Inactivation of the tuberous sclerosis complex-1 and –2 gene products occurs by phosphoinositide 3-kinase/Akt-dependent and –independent phosphorylation of tuberin. J. Biol. Chem. 2003; 278:37288-37296. (PDF)
Fingar D, Richardson C, Tee A, Cheatham L, Tsou C and Blenis J. mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4EBP1/eIF4E. Mol. Cell Biol. 2004. 24: 200-216 . (PDF)
Tee AR, Tee JA and Blenis J. Characterizing the interaction of the mammalian eIF4E-related translation initiation factor 4EHP with 4E-BP1. FEBS Lett. 2004; 564: 58-62.
McMullen JR, Shioi T, Zhang L, Tarnavski O, Sherwood MC, Dorfman AL, Longnus S, Pende M, Martin KA, Blenis J, Thomas G, Izumo S. Deletion of ribosomal S6 kinases does not attenuate pathological, physiological, or insulin-like growth factor 1 receptor-phosphoinositide 3-kinase-induced cardiac hypertrophy.Mol Cell Biol. 2004; 24: 6231-6240.
Richardson CJ, Broenstrup M, Fingar DC, Jülich K, Ballif BA, Gygi SP and Blenis J. SKAR is a specific target of S6 kinase 1 in cell growth control. Current Biology 2004; 14: 1540-1549 . (PDF)
Schalm* SS, Tee* AR and Blenis J. Characterization of a conserved C-terminal (RSPRR) motif in S6K1 required for its mTOR-dependent regulation. J. Biol. Chem. 2005; 280:11101-11106 . (PDF)
Holz MK, Blenis J. Identification of S6K1 as a novel mTOR-phosphorylating kinase. J. Biol. Chem. 2005; 280:26089-26093. (PDF)
Signaling during cellular stress response and programmed cell death
Tung RM and Blenis J. A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase. Oncogene 1997; 14: 653-659.
Juo P, Kuo CJ, Reynolds SE, Konz RF, Raengeaud J, Davis RJ, Biemann H-B and Blenis J. Fas activation of the p38 MAP kinase signalling pathway requires ICE/CED-3 family proteases. Mol. Cell Biol. 1997; 17: 24-35.
Schinkmann K and Blenis J. Cloning and characterization of a human STE20-like protein kinase with unusual cofactor requirements. J. Biol. Chem. 1997; 272: 28695-28703.
Oehrl W, Kardinal C, Ruf S, Adermann K, Groffen J, Feng G-S, Blenis J, Tan T-H and Feller MS. The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins. Oncogene 1998; 8: 1893-1901.
Juo P, Kuo CJ, Yuan J and Blenis J. Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Current Biol. 1998; 8: 1001-1008.
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J and Greenberg ME. Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell 1999; 96: 857-868.
Sanchez I, Xu C-J, Juo P, Kakizaka A, Blenis J and Yuan J. Caspase-8 is required for cell death by expanded polyglutamine repeats. Neuron 1999; 22: 623-633.
Juo P, Woo MS-A, Kuo CJ, Signorelli P, Biemann HP, Hannun YA and Blenis J. FADD is required for multiple signaling events downstream of the receptor Fas. Cell Growth & Diff. 1999: 10: 797-804.
Shimamura A, Ballif BA, Richards SA and Blenis J. RSK1 mediates a MEK/MAP kinase cell survival signal. Current Biology, 2000; 10: 127-135. (PDF)
Bodmer JL, Holler N, Reynard S, Vinciguerra P, Schneider P, Juo P, Blenis J and Tschopp J. TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol. 2000; 2 :241-243.
Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J, Krammer PH and Walczak H. FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity. 2000; 12: 599-609.
Ding HF, Lin YL, McGill G, Juo P, Shu H, Blenis J, Yuan J and Fisher DE. Essential role for caspase-8 in transcription-independent apoptosis triggered by p53. J Biol Chem. 2000; 275: 38905-38911.
Verhey KJ, Meyer D, Deehan R, Blenis J, Schnapp BJ, Rapoport T and Margolis B. Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J Cell Biol. 2001; 152: 959-970.
Cell Survival and Cell Death Signaling.
MacKeigan* JP, Murphy* LO, Blenis J. Sensitized RNAi screen of human kinases and phosphatases identifies novel regulators of apoptosis and chemoresistance. Nat. Cell Biol. 2005; 7: 591-600. (PDF). See commentary in Cancer Cell (PDF)
Reviews
Blenis J. MAP kinases: Proceed at your own RSK. Proc. Natl. Acad. Sci. USA 1993; 90:5889-5892.
Chou MM and Blenis J. The 70kD S6 kinase: Regulation of a kinase with multiple roles in mitogenic signalling. Current Opinions in Cell Biology, 1995; 7: 806-814.
Grammer TC, Cheatham L, Chou MM and Blenis J. The pp70S6k signalling pathway: A novel signalling system involved in growth regulation. in Cancer Surveys, 1996.
Ballif BA and Blenis J. Molecular Mechanisms Mediating Mammalian MEK-MAPK Cell Survival Signals. Cell Growth & Diff. 2001; 12: 397-408 (PDF)
Martin, K. A. and Blenis, J. Coordinate regulation of the PI 3-Kinase and mTOR pathways in translational control. Advances in Cancer Research 2002 Vol. 86 Chapter 1, pages 1-39. (PDF)
Richardson CR, Schalm SS and Blenis J. PI3-Kinase and TOR: PIKTORing Cell Growth. In: Seminars in Cell and Developmental Biology 2004; 15: pp. 147-159. (PDF)
Roux P and Blenis J. The ERK- and p38 MAPK-activated protein kinases (MKs): A family of protein kinases with diverse biological functions. In: Microbiology and Molecular Biology Reviews 2004; 68: pp. 320-344. (PDF)
Fingar D and Blenis J. Target of rapamycin: An integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 2004; 23: pp. 3151-3171. (PDF)
Tee AR and Blenis J. mTOR, translational control and human disease. In: Seminars in Cell & Developmental Biology 2005; 16: pp 29–37. (PDF)