Novel mechanisms of endothelial mechanotransduction

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 34, Issue 11, 2014, Pages 2378-2386

  Abe, Jun Ichi ^a,b   Berk, Bradford C ^a  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

ERK5; flow; PK ; SUMOylation

Indexed keywords

ENDOTHELIAL NITRIC OXIDE SYNTHASE; KRUPPEL LIKE FACTOR 2; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 7; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PROTEIN KINASE C ZETA; PROTEIN P53; PROTEIN P90; S6 KINASE;

APOPTOSIS; ARTERY BLOOD FLOW; ATHEROGENESIS; ATHEROSCLEROSIS; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; ENZYME ACTIVITY; GENE EXPRESSION; HUMAN; LAMINAR FLOW; MECHANOTRANSDUCTION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVIEW; SUMOYLATION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; VASCULAR ENDOTHELIUM; ANIMAL; BIOMECHANICS; DISEASE MODEL; PATHOPHYSIOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; VASCULAR REMODELING;

ANIMALS; ATHEROSCLEROSIS; BIOMECHANICAL PHENOMENA; DISEASE MODELS, ANIMAL; ENDOTHELIUM, VASCULAR; HUMANS; MECHANOTRANSDUCTION, CELLULAR; MITOGEN-ACTIVATED PROTEIN KINASE 7; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; SIGNAL TRANSDUCTION; VASCULAR REMODELING;

EID: 84911941197     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.114.303428     Document Type: Review

References (98)

1. Won D, Zhu SN, Chen M, Teichert AM, Fish JE, Matouk CC, Bonert M, Ojha M, Marsden PA, Cybulsky MI. Relative reduction of endothelial nitric-oxide synthase expression and transcription in atherosclerosis-prone regions of the mouse aorta and in an in vitro model of disturbed flow. Am J Pathol. 2007;171:1691-1704.
2. Jongstra-Bilen J, Haidar i M, Zhu SN, Chen M, Guha D, Cybulsky MI. Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med. 2006;203:2073-2083.
3. Bao X , Lu C, Frangos JA. Temporal gradient in shear but not steady shear stress induces PDGF-A and MCP-1 expression in endothelial cells: role of NO, NF kappa B, and egr-1. Arterioscler Thromb Vasc Biol. 1999;19:996-1003.
4. Wang GX, Cai SX, Wang PQ, Ouyang KQ, Wang YL, Xu SR. Shearinduced changes in endothelin-1 secretion of microvascular endothelial cells. Microvasc Res. 2002;63:209-217.
5. Hsiai TK, Cho SK, Reddy S, Hama S, Navab M, Demer LL, Honda HM, Ho CM. Pulsatile flow regulates monocyte adhesion to oxidized lipid-induced endothelial cells. Arterioscler Thromb Vasc Biol. 2001; 21:1770-1776.
6. Frangos JA, Eskin SG, McIntire LV, Ives CL. Flow effects on prostacyclin production by cultured human endothelial cells. Science. 1985;227:1477-1479.
7. Di Francesco L, Totani L, Dovizio M, Piccoli A, Di Francesco A, Salvatore T, Pandolfi A, Evangelista V, Dercho RA, Seta F, Patrignani P. Induction of prostacyclin by steady laminar shear stress suppres ses tumor necrosis factor-alpha biosynthesis via heme oxygenase-1 in human endothelial cells. Circ Res. 2009;104:506-513.
8. Korenaga R, Ando J, Tsuboi H, Yang W, Sakuma I, Toyo-oka T, Kam iya A. Laminar flow stimulates ATP-and shear stress-dependent nitric oxide production in cultured bovine endothelial cells. Biochem Biophys Res Commun. 1994;198:213-219.
9. Diamond SL, Eskin SG, McIn tire LV. Fluid flow stimulates tissue plasminogen activator secretion by cultured human endothelial cells. Science. 1989;243:1483-1485.
10. Gimbrone MA Jr, Topper JN, Nagel T, Anderson KR, Garcia-Cardeñ a G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci. 2000;902:230-9; discussion 239.
11. Hsieh HJ, Li NQ, Frangos JA. Pulsatile and steady flow induces c-fos expression in human endothelial cells. J Cell Physiol. 1993;154:143-151.
12. Khachigian LM, Resnick N, Gimbrone MA Jr, Collins T. Nuclear factor-kappa B interacts functionally with the platelet -derived growth factor B-chain shear-stress response element in vascular endothelial cells exposed to fluid shear stress. J Clin Invest. 1995;96:1169-1175.
13. Lan Q, Mercurius KO, Davies PF. Stimula tion of transcription factors NF kappa B and AP1 in endothelial cells subjected to shear stress. Biochem Biophys Res Commun. 1994;201:950-956.
14. Heo KS, Fujiwara K, Abe J. Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. Circ J. 2011;75:2722-2730.
15. Abe J, Baines CP, Berk BC. Role of mitogen-activated protein kinases in ischemia and reperfusion injury: the good and the bad [editorial; comment]. Circ Res. 2000;86:607-609.
16. Abe J, Berk BC. Reactive oxygen species as mediators of signal transduction in cardiovascular disease. Trends Cardiovasc Med. 1998;8:59-64.
17. Yan C, Takahashi M, Okuda M, Lee JD, Berk BC. Fluid shear stress stimulates big mitogen-activated pro tein kinase 1 (BMK1) activity in endothelial cells. Dependence on tyrosine kinases and intracellular calcium. J Biol Chem. 1999;274:143-150.
18. Zhou G, Bao ZQ, Dixon JE. Components of a new human protein kinase signal transduction pathway. J Biol Chem. 1995;270:12665-12669.
19. English JM, Vanderbilt CA, Xu S, Marcus S, Cobb MH. Isolation of MEK5 and differential expression of alternatively spliced forms. J Biol Chem. 1995;270:28897-28902.
20. De Cesaris P,Starace D,Starace G,Filippini A,Stefanini M,Ziparo E. Activation of Jun N-terminal kinase/stress-activated pro tein kinase pathway by tumor necrosis factor alpha leads to intercellular adhesion molecule-1 expression. J Biol Chem. 1999;274:28978-28982.
21. Ahmad M, Theofanidis P, Medford RM. Role of activating protein-1 in the regulation of the vascular cell adhesion molecule-1 gene expression by tumor necrosis factor-alpha. J Biol Chem. 1998;273:4616-4621.
22. Min W, Pober JS. TNF initiates E-selectin transc ription in human endothelial cells through parallel TRAF-NF-kappa B and TRAF-RAC/CDC42-JNK-c-Jun/ATF2 pathways. J Immunol. 1997;159:3508-3518.
23. Wong HK, Fricker M, Wyttenbach A, Villunger A, Mi chalak EM, Strasser A, Tolkovsky AM. Mutually exclusive subsets of BH3-only proteins are activated by the p53 and c-Jun N-terminal kinase/c-Jun signaling pathways during cortical neuron apoptosis induced by arsenite. Mol Cell Biol. 2 005;25:8732-8747.
24. Fan G, Merritt SE, Kortenjann M, Shaw PE, Holzman LB. Dual leucine zipper-bearing kinase (DLK) activates p46SAPK and p38mapk but not ERK2. J Biol Chem. 1996;271:24788-24793.
25. Li L, Tatake RJ, Natarajan K, Taba Y, Garin G, Tai C, Leung E, Surapisitchat J, Yoshizumi M, Yan C, Abe J, Berk BC. Fluid shear stress inhibits TNF-mediated JNK act ivation via MEK5-BMK1 in endothelial cells. Biochem Biophys Res Commun. 2008;370:159-163.
26. Akaike M, Che W, Marmarosh NL, Ohta S, Osawa M, Ding B, Berk BC, Yan C, Abe J. Th e hinge-helix 1 region of peroxisome proliferatoractivated receptor gamma1 (PPARgamma1) mediates interaction with extracellular signal-regulated kinase 5 and PPARgamma1 transcriptional activation: involvement in flow-induced PPARgamma activation in endoth elial cells. Mol Cell Biol. 2004;24:8691-8704.
27. Kasler HG, Victoria J, Duramad O, Winoto A. ERK5 is a novel type of mitogen-activated protein kinase containing a transcriptional activation doma in. Mol Cell Biol. 2000;20:8382-8389.
28. Pi X, Garin G, Xie L, Zheng Q, Wei H, Abe J, Yan C, Berk BC. BMK1/ERK5 is a novel regulator of angiogenesis by destabilizing hypoxia indu cible factor 1alpha. Circ Res. 2005;96:1145-1151.
29. Lee JD, Ulevitch RJ, Han J. Primary structure of BMK1: a new mammalian map kinase. Biochem Biophys Res Commun. 1995;213:715-724.
30. Hayashi M, Kim SW, Imanaka-Yoshida K, Yoshida T, Abel ED, Eliceiri B, Yang Y, Ulevitch RJ, Lee JD. Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial fa ilure. J Clin Invest. 2004;113:1138-1148.
31. Parmar KM, Larman HB, Dai G, Zhang Y, Wang ET, Moorthy SN, Kratz JR, Lin Z, Jain MK, Gimbrone MA Jr, García-Cardeña G. In tegration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J Clin Invest. 2006;116:49-58.
32. Schulman IG, Juguilon H, Evans RM. Activation and repression by nuclear hormone recepto rs: hormone modulates an equilibrium between active and repressive states. Mol Cell Biol. 1996;16:3807-3813.
33. Hu X, Lazar MA. The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors. Nature. 1999;402:93-96.
34. Piqueras L, Sanz MJ, Perretti M, Morcillo E, Norling L, Mitchell JA, Li Y, Bishop-Bailey D. Activation of PPARbeta/delta inhibits leukocyt e recruitment, cell adhesion molecule expression, and chemokine release. J Leukoc Biol. 2009;86:115-122.
35. Takata Y, Liu J, Yin F, Collins AR, Lyon CJ, Lee CH, Atkins AR, Downes M, Barish GD, Evans RM, Hsueh WA, Tangirala RK. PPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis. Proc Natl Acad Sci U S A. 2008;105:4277-4282.
36. Wang N, Verna L, Chen NG, Chen J, Li H, Forman BM, Stemerman MB. Constitutive activation of peroxisome proliferator-activated receptorgamma suppresses pro-inflammatory adhesion molecules in human vascular endothelial cells. J Biol Chem. 2002;277:34176-34181.
37. Camp HS, Tafuri SR. Regulation of peroxisome proliferator-activated receptor gamma activity by mitogen-activated protein kinase. J Biol Chem. 1997;272:10811-10816.
38. Barish GD, Yu RT, Karunasiri MS, et al. The bcl6-smrt/ncor cistrome represses inflammation to attenuate atherosclerosis. Cell Metab. 2012;15:554-562
39. . Lee CH, Chawla A, Urbiztondo N, Liao D, Boisvert WA, Evans RM, Curtiss LK. Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science. 2003;302:453-457.
40. Glass CK, Saijo K. Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat Rev Immunol. 2010;10:365-376.
41. Straus DS, Glass CK. Anti-inf lammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol. 2007;28:551-558.
42. Ricote M,Glass CK. PPARs and molecular mechanisms of transrepression. Biochim Biophys Acta. 2007;1771:926-935.
43. Pascual G, Glass CK. Nuclear receptors versus inflammation: mechanisms of transrepression. Trends Endocrinol Metab. 2006;17:321-327.
44. Woo CH, Massett MP, Shishido T, Itoh S, Ding B, McClain C, Che W, Vulapalli SR, Yan C, Abe J. ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor delta (PPARdelta) stimulation. J Biol Chem. 2006;281:32164-32174.
45. Suzuki T, Aizawa K, Matsumura T, Nagai R. Vascular implications of the Krüppel-like family of transcription factors. Arteriosc ler Thromb Vasc Biol. 2005;25:1135-1141.
46. Dekker RJ, van Soest S, Fontijn RD, Salamanca S, de Groot PG, VanBavel E, Pannekoek H, Horrevoets AJ. Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Krüppel-like factor (KLF2). Blood. 2002;100:1689-1698.
47. Rothwarf DM, Karin M. The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleus. Sci STKE. 1999;1999:RE1.
48. SenBanerjee S, Lin Z, Atkins GB, Greif DM, Rao RM, Kumar A, Feinberg MW, Chen Z, Simon DI, Luscinskas FW, Michel TM, Gimbrone MA Jr, Garcí a-Cardeña G, Jain MK. KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med. 2004;199:1305-1315.
49. Sen-Banerjee S, Mir S, Lin Z, Hamik A, Atkins GB, Das H, Banerjee P, Kumar A, Jain MK. Kruppel-like factor 2 as a novel mediator of statin effects in endothelial cells. Circulation. 2005;112:720-726.
50. Lin Z, Natesan V, Shi H, Dong F, Kawanami D, Mahabeleshwar GH, Atkins GB, Nayak L, Cui Y, Finigan JH, Jain MK. Kruppel-like factor 2 regulates endothelial barrier function. Arterioscler Thromb Vasc Biol. 2010;30:1952- 1959.
51. Sohn SJ, Sarvis BK, Cado D, Winoto A. ERK5 MAPK regulates embryonic angiogenesis and acts as a hypoxia-sensitive repressor of vascular endothelial growth factor expression. J Biol Chem. 2002;277:43344-43351.
52. Le NT, Heo KS, Takei Y, et al. A crucial role for p90rsk-mediated reduction of erk5 transcriptional activity in endothelial dysfunction and a therosclerosis. Circulation. 2013;127:486-499
53. Heo KS, Lee H, Nigro P, Thomas T, Le NT, Chang E, McClain C, Reinhart-King CA, King MR, Berk BC, Fujiwara K, Woo CH, Abe J. PKC?mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation. J Cell Biol. 2011;193:867-884.
54. Le NT, Corsetti JP, Dehoff-Sparks JL, Sparks CE, Fujiwara K, Abe J. Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation. Int J Inflam. 2012;2012:678190.
55. Woo CH, Abe J. SUMO-A post-translational modification with therapeutic potential?Curr Opin Pharmacol. 2010;10:146-155.
56. Hickey CM, Wilson NR, Hochstrasser M. Function and regulation of SUMO proteases. Nat Rev Mol Cell Biol. 2012;13:755-766.
57. Johnson ES, Schwienhorst I, Dohmen RJ, Blobel G. The ubiquitin-like protein Smt3p is activated for conjugation to other proteins by an Aos1p/Uba2p heterodimer. EMBO J. 1997;16:5509-5519.
58. Johnson ES, Blobel G. Ubc9p is the conjugating enzyme for the ubiquitinlike protein Smt3p. J Biol Chem. 1997;272:26799-26802.
59. Johnson ES. Protein modification by SUMO. Annu Rev Biochem. 2004;73:355-382.
60. Li SJ, Hochstrasser M. A new protease required for cell-cycle progression in yeast. Nature. 1999;398:246-251.
61. Yeh ET. SUMOylation and De-SUMOylation: wrestling with life's processes. J Biol Chem. 2009;284:8223-8227.
62. Chang E, Heo KS, Woo CH, Lee H, Le NT, Thomas TN, Fujiwara K, Abe J. MK2 SUMOyla tion regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation. Blood. 2011;117:2527-2537.
63. Woo C.H.,Shishido T,Mc Clain C,Lim JH,Li JD,Yang J,Yan C,Abe J. Extracellular signal-regulated kinase 5 SUMOylation antagonizes shear stress-induced antiinflammatory response and endothelial nitric oxide synthase expression in endothelial cells. Circ Res. 2008;102:538-545.
64. Nigro P, Abe J, Woo CH, Satoh K, McClain C, O'Dell MR, Lee H, Lim JH, Li JD, Heo KS, Fujiwara K, Berk BC. PKCzeta decreases eNOS protein stabilit y via inhibitory phosphorylation of ERK5. Blood. 2010;116:1971- 1979.
65. Heo KS, Chang E, Le NT, Cushman H, Yeh ET, Fujiwara K, Abe J. De-SUMOylation enzyme of sentrin/SUMO-specific protease 2 regulates disturbed flow-induced SUMOylation of ERK5 and p53 that leads to endothelial dysfunction and atherosclerosis. Circ Res. 2013;112:911-923.
66. Chiu YJ, Kusano K, Thomas TN, Fujiwara K. Endothelial cell-cell adhesion and mechanosignal transduction. Endothelium. 2004;11:59-73.
67. Garner E, Raj K. Protective mechanisms of p53-p21-pRb proteins against DNA damage-induced cell death. Cell Cycle. 2008;7:277-282.
68. Lin K, Hsu PP, Chen BP, Yuan S, Usami S, Shyy JY, Li YS, Chien S. Molecular mechanism of endothelial growth arrest by laminar shear stress. Proc Natl Acad Sci U S A. 2000;97:9385-9389.
69. Carter S, Bischof O, Dejean A, Vousden KH. C-terminal modifications regulate MDM2 dissociation and nuclear export of p53. Nat Cell Biol. 2007;9:428-435.
70. Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM. p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 2003;11:577-590.
71. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene . 1994;9:1799-1805.
72. Heo KS, Lee H, Nigro P, Thomas T, Le NT, Chang E, McClain C, Reinhart-King CA, King MR, Berk BC, Fujiwara K, Woo CH, Abe J. PKC?mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation. J Cell Biol. 2011;193:867-884.
73. Magid R, Davies PF. Endothelial protein kinase C isoform identity and differential activity of PKCzeta in an athero-susceptible region of porcine aorta. Circ Res. 2005;97:443-449.
74. Frey RS, Rahman A, Kefer JC, Minshall RD, Malik AB. PKCzeta regulates TNF-alpha-induced activation of NADPH oxidase in endothelial cells. Circ Res. 2002;90:1012-1019.
75. Nigro P, Abe JI, Woo CH, Satoh K, McClain C, O'Dell MR, Lee H, Lim JH, Li JD, Heo KS, Fujiwara K, Berk BC. Pkc{zeta} decreases enos protein stability via inhibitory phosphorylation of erk5. Blood. 2010
76. Newton AC. Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem Rev. 2001;101:2353-2364.
77. Smith L, Wang Z, Smith JB. Caspase processing activates atypical protein kinase C zeta by relieving autoinhibition and destabilizes the protein. Biochem J. 2003;375(Pt 3):663-671 .
78. Averna M, Stifanese R, De Tullio R, Passalacqua M, Salamino F, Pontremoli S, Melloni E. Functional role of HSP90 complexes with endothelial nitric-oxide synthase (eNOS) and calpain on nitric oxide g eneration in endothelial cells. J Biol Chem. 2008;283:29069-29076.
79. Dong Y, Wu Y, Wu M, Wang S, Zhang J, Xie Z, Xu J, Song P, Wilson K, Zhao Z, Lyons T, Zou MH. Activation of protease calpain by oxidized and glycated ldl increases the degradation of endothelial nitric oxide synthase. Journal of cellular and molecular medicine. 2009;13:2899-2910
80. Kim GY, Nigro P, Fujiwara K, Abe J, Berk BC. p62 binding to protein kinase C?regulates tumor necrosis factor?-induced apoptotic pathway in endothelial cells. Arterioscler Thromb Vasc Biol. 2012;32:2974-2980.
81. Moscat J, Diaz-Meco MT, Wooten MW. Of the atypical PKCs, Par-4 and p62: recent understandings of the biology and pathology of a PB1-dominated complex. Cell Death Differ. 2009;16:1426-1437.
82. Kang X, Qi Y , Zuo Y, Wang Q, Zou Y, Schwartz RJ, Cheng J, Yeh ET. SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development. Mol Cell. 2010;38:191-201.
83. Li X, Luo Y, Yu L, Lin Y, Luo D, Zhang H, He Y, Kim YO, Kim Y, Tang S, Min W. SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1- dependent apoptosis. Cell Death Differ. 2008;15:739-750.
84. Cheng J,Kang X,Zhang S,Yeh ET. SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell. 2007;131: 584-595.
85. Frö din M, Gammeltoft S. Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol. 1999;151:65-77.
86. Ranganathan A, Pearson GW, Chrestensen CA, Sturgill TW, Cobb MH. The MAP kinase ERK5 binds to and phosphorylates p90 RSK. Arch Biochem Biophys. 2006;449:8-16.
87. Le NT, Takei Y, Shis hido T, et al. P90rsk targets the erk5-chip ubiquitin e3 ligase activity in diabetic hearts and promotes cardiac apoptosis and dysfunction. Circ Res. 2012;110:536-550
88. Zhao Y, Bjorbaek C, Mol ler DE. Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases. J Biol Chem. 1996;271:29773-29779.
89. Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW. Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo. J Biol Ch em. 1999;274:2893-2898.
90. Blenis J. Signal transduction via the MAP kinases: proceed at your own RSK. Proc Natl Acad Sci U S A. 1993;90:5889-5892.
91. Abe J, Okud a M, Huang Q, Yoshizumi M, Berk BC. Reactive oxygen species activate p90 ribosomal S6 kinase via Fyn and Ras. J Biol Chem. 2000;275:1739-1748.
92. Chen RH, Sarnecki C, Blenis J. Nuclear localization and regulation of erkand rsk-encoded protein kinases. Mol Cell Biol. 1992;12:915-927.
93. Chen RH, Tung R, Abate C, Blenis J. Cytoplasmic to nuclear signal transduction by mitoge n-activated protein kinase and 90 kDa ribosomal S6 kinase. Biochem Soc Trans. 1993;21:895-900.
94. Ghoda L, Lin X, Greene WC. The 90-kDa ribosomal S6 kinase (pp90rsk) phosphorylates the N-terminal re gulatory domain of IkappaBalpha and stimulates its degradation in vitro. J Biol Chem. 1997;272:21281-21288.
95. Chen RH, Chung J, Blenis J. Regulation of pp90rsk phosphorylation and S6 phosphotransfe rase activity in Swiss 3T3 cells by growth factor-, phorbol ester-, and cyclic AMP-mediated signal transduction. Mol Cell Biol. 1991;11:1861-1867.
96. Fisher TL, Blenis J. Evidence for two catalytically active kinase domains in pp90rsk. Mol Cell Biol. 1996;16:1212-1219.
97. Xing J, Ginty DD, Greenberg ME. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science. 1996;273:959-963.
98. Pearson G, English JM, White MA, Cobb MH. Erk5 and erk2 cooperate to regulate nf-{kappa}b and cell transformation. J Biol Chem. 2000;15:15