The raf/mek/erk signal transduction cascade as a target for chemotherapeutic intervention in leukemia

Leukemia

Volumn 16, Issue 4, 2002, Pages 486-507

  Lee, J T ^a   McCubrey, J A ^a  

^a EAST CAROLINA UNIVERSITY   (United States)

Author keywords

Akt; Erk; Il 3; Inhibitors; Leukemia; Mek; Oncogenes; P13K; Phosphatase; Raf; Ras; Signal transduction; Transcription factor

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 3 BENZYL 7 CYANO 2,3,4,5 TETRAHYDRO 1 (1H IMIDAZOL 4 YLMETHYL) 4 (2 THIENYLSULFONYL) 1H 1,4 BENZODIAZEPINE; 4 (4 HYDROXYANILINO) 6,7 DIMETHOXYQUINAZOLINE; 6,7 DIMETHOXY 2 PHENYLQUINOXALINE; ANTINEOPLASTIC AGENT; GELDANAMYCIN; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR RECEPTOR; IMATINIB; INTERLEUKIN 3 RECEPTOR; KF 25706; L 778123; LEFLUNOMIDE; LONAFARNIB; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE KINASE; N BENZYL 2 CYANO 3 (3,4 DIHYDROXYPHENYL)ACRYLAMIDE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN INHIBITOR; PROTEIN KINASE C INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; RADICICOL; RAF PROTEIN; STAUROSPORINE; TIPIFARNIB; TRANSCRIPTION FACTOR; UCN 101; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CELL FATE; CELL GROWTH; CELL PROLIFERATION; CELL SURVIVAL; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVATION; GENE EXPRESSION; HUMAN; HUMAN CELL; LEUKEMIA; LEUKEMIA CELL; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

EID: 0036238817     PISSN: 08876924     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj/leu/2402460     Document Type: Review

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178. A derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and in vitro anti-proliferative, as well as in vivo anti-tumor activity
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189. Isolation of MEK5 and differential expression of alternatively spliced forms
190. A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function
191. Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues
192. B-Raf protein isoforms interact with and phosphorylate Mek-1 on serine residues 218 and 222
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194. Transformation of mammalian cells by constitutively active MAP kinase kinase
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197. A conditionally active form of MEK1 results in autocrine transformation of human and mouse hematopoietic cells
198. Combined effects of aberrant MEK1 activity and BCL2 overexpression on relieving the cytokine-dependency of hematopoietic cells
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208. Identification of a novel inhibitor of mitogen-activated protein kinase kinase
209. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo
210. Development of anticancer drugs targeting the MAP kinase pathway
211. Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells
212. Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3
213. UVB activates ERK1/2 and p38 signaling pathways via reactive oxygen species in cultured keratinocytes
214. Hydrogen peroxide activation of multiple mitogen-activated protein kinases in an oligodendrocyte cell line: Role of extracellular signal-regulated kinase in hydrogen peroxide-induced cell death
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235. A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1
236. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase
237. pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167
238. IkappaB alpha is a target for the mitogen-activated 90 kDa ribosomal S6 kinase
239. The 90-kDa ribosomal S6 kinase (pp90rsk) phosphorylates the N-terminal regulatory domain of IkappaBalpha and stimulates its degradation in vitro
240. Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase
241. Transcription factors and translocations in lymphoid and myeloid leukemia
242. CREB and its associated proteins act as survival factors for human melanoma cells
243. Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB
244. Granulocyte-macrophage colony-stimulating factor and interleukin-3 signaling pathways converge on the CREB-binding site in the human egr-1 promoter
245. Insulin-like growth factor-1 induces bcl-2 promoter through the transcription factor cAMP-response element-binding protein
246. The molecular role of Myc in growth and transformation: Recent discoveries lead to new insights
247. Identification of target genes of oncogenic transcription factors
248. c-Myc represses transcription in vivo by a novel mechanism dependent on the initiator element and Myc box II
249. Repression of cyclin D1: A novel function of MYC
250. c-Myc transactivates the p53 promoter through a required downstream CACGTG motif
251. An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc
252. The ornithine decarboxylase gene is a transcriptional target of c-Myc
253. Ets transcription factors and human disease
254. Ets-1 regulates angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells
255. Androgen receptor-Ets protein interaction is a novel mechanism for steroid hormone-mediated down-modulation of matrix metalloproteinase expression
256. Ets up-regulates MET transcription
257. Transactivation of the P2 promoter of parathyroid hormone-related protein by human T-cell lymphotropic virus type 1 Tax1: Evidence for the involvement of transcription factor Ets1
258. AP-1 in cell proliferation and survival
259. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40
260. Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation
261. Expression of a downregulated target, SSeCKS, reverses v-Jun-induced transformation of 10T1/2 murine fibroblasts
262. Transcriptional control of SPARC by v-Jun and other members of the AP1 family of transcription factors
263. Diverse agents act at multiple levels to inhibit the Rel/NF-kappaB signal transduction pathway
264. Regulation of DNA binding by Rel/NF-kappaB transcription factors: Structural views
265. The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L)
266. NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene
267. Transactivation of the c-myc gene by HTLV-1 tax is mediated by NFkB
268. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1
269. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase
270. Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation
271. Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism
272. Phosphorylated CREB binds specifically to the nuclear protein CBP
273. AP-1: Introductory remarks
274. Regulation of the MAP kinase pathway by mammalian Ksr through direct interaction with MEK and ERK
275. Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73
276. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain
277. JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
278. c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases
279. Inhibition of c-Jun DNA binding by mitogen-activated protein kinase
280. Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73
281. Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain
282. Transformation suppressor activity of a Jun transcription factor lacking its activation domain
283. Cellular transformation and malignancy induced by ras require c-jun
284. Analysis of AP-1 function in cellular transformation pathways
285. Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase
286. Phosphorylation of c-Fos at the C-terminus enhances its transforming activity
287. Signal transduction by the c-Jun N-terminal kinase
288. Distinct roles of Jun: Fos and Jun: ATF dimers in oncogenesis
289. Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-jun promoter and to cellular transformation
290. Rel/NF-kappa B/I kappa B family: Intimate tales of association and dissociation
291. Activators and target genes of Rel/NF-kappaB transcription factors
292. Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway
293. NF-kappa B: Ten years after
294. Raf-1 protein kinase activates the NF-kappa B transcription factor by dissociating the cytoplasmic NF-kappa B-I kappa B complex
295. The 90-kDa ribosomal S6 kinase (pp90rsk) phosphorylates the N-terminal regulatory domain of IkappaBalpha and stimulates its degradation in vitro
296. IkappaB alpha is a target for the mitogen-activated 90 kDa ribosomal S6 kinase
297. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells
298. Identification of the c-myc oncogene product in normal and malignant B cells
299. The protein encoded by the human proto-oncogene c-myc
300. The role of c-myc in cellular growth control
301. The Myc/Max/Mad network and the transcriptional control of cell behavior
302. Inhibition of cell proliferation by the Mad1 transcriptional repressor
303. The Max network gone mad
304. MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer
305. MM-1, a novel c-Myc-associating protein that represses transcriptional activity of c-Myc
306. A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression
307. Signal transduction within the nucleus by mitogen-activated protein kinase
308. c-Myc transactivation domain-associated kinases: Questionable role for map kinases in c-Myc phosphorylation
309. The transactivation potential of a c-Myc N-terminal region (residues 92-143) is regulated by growth factor/Ras signaling
310. Ras enhances Myc protein stability
311. Regulation of c-myc expression by Ras/Raf signalling
312. Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase
313. Ets transcription factors: Nuclear effectors of the Ras-MAP-kinase signaling pathway
314. The Ets family of transcription factors
315. Ets target genes: Past, present and future
316. Signal transduction and the Ets family of transcription factors
317. The ETS domain protein pointed-P2 is a target of MAP kinase in the sevenless signal transduction pathway
318. Ras/MAP kinase-dependent and -independent signaling pathways target distinct ternary complex factors
319. Transient activation of RAF-1, MEK, and ERK2 coincides kinetically with ternary complex factor phosphorylation and immediate-early gene promoter activity in vivo
320. Protein phosphatases and the regulation of mitogen-activated protein kinase signalling
321. Dual specificity phosphatases: A gene family for control of MAP kinase function
322. MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo
323. Isolation and characterisation of a uniquely regulated threonine, tyrosine phosphatase (TYP 1) which inactivates ERK2 and p54jnk
324. Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase
325. The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases
326. MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase
327. Molecular cloning and functional characterization of a novel mitogen-activated protein kinase phosphatase, MKP-4
328. Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5
329. MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases
330. A novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs
331. Negative-feedback regulation of CD28 costimulation by a novel mitogen-activated protein kinase phosphatase, MKP6
332. The dual specificity mitogen-activated protein kinase phosphatase-1 and -2 are induced by the p42/p44MAPK cascade
333. Feedback regulation of Raf-1 and mitogen-activated protein kinase (MAP) kinase kinases 1 and 2 by MAP kinase phosphatase-1 (MKP-1)
334. Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase
335. Compartment-specific regulation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) by ERK-dependent and non-ERK-dependent inductions of MAPK and MKP-1 in differentiating P19 cells
336. Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism
337. The structure of protein phosphatase 2A is as highly conserved as that of protein phosphatase 1
338. Protein phosphatase 2A positively and negatively regulates Ras1-mediated photoreceptor development in Drosophila
339. Inhibition of protein phosphatase PP1 in GH3B6, but not in GH3 cells, activates the MEK/ERK/c-fos pathway and the human prolactin promoter, involving the coactivator CPB/p300
340. Protein phosphatase 2A suppresses MAP kinase signalling and ectopic protein expression
341. Role of protein phosphatase 2A in the regulation of mitogen-activated protein kinase activity in ventricular cardiomyocytes
342. Protein phosphatases 1 and 2A promote Raf-1 activation by regulating 14-3-3 interactions
343. Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation
344. Differential induction of apoptosis in human breast tumor cells by okadaic acid and related inhibitors of protein phosphatases 1 and 2A
345. Phosphatidylinositol 3-kinase: Structure and expression of the 110 kd catalytic subunit
346. The C-terminal SH2 domain of p85 accounts for the high affinity and specificity of the binding of phosphatidylinositol 3-kinase to phosphorylated platelet-derived growth factor beta receptor
347. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate
348. Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B
349. Mechanism of activation of protein kinase B by insulin and IGF-1
350. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): Structural and functional homology with the Drosophila DSTPK61 kinase
351. The akt kinase: Molecular determinants of oncogenicity
352. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha
353. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
354. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt
355. Regulation of cell death protease caspase-9 by phosphorylation
356. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor
357. Induction of NF-kappaB by the Akt/PKB kinase
358. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer
359. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
360. Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways
361. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate
362. The lipid phosphatase activity of PTEN is critical for its tumor suppressor function
363. Pten is essential for embryonic development and tumour suppression
364. Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems
365. Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: The role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses
366. Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase
367. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)
368. 3-(Hydroxymethyl)-bearing phosphatidylinositol either lipid analogues and carbonate surrogates block PI3-K, Akt, and cancer cell growth
369. Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation
370. Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor
371. Akt/PKB activity is required for Ha-Ras-mediated transformation of intestinal epithelial cells
372. Apoptosis suppression by Raf-1 and MEK1 requires MEK- and phosphatidylinositol 3-kinase-dependent signals
373. Interactions between the PI3K and Raf signaling pathways can result in the transformation of hematopoietic cells
374. Regulation of Raf by Akt controls growth and differentiation in vascular smooth muscle cells
375. Negative regulation of the serine/threonine kinase B-Raf by Akt
376. Phosphorylation and regulation of Raf by Akt (protein kinase B)
377. Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt
378. Phosphorylation of Bcl2 and regulation of apoptosis
379. Ceramide regulates cellular homeostasis via diverse stress signaling pathways