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Extracellular-regulated Protein Kinase (extracellular-regulated + protein_kinase)
Selected AbstractsPhage display identifies novel peptides that bind extracellular-regulated protein kinase 2 to compete with transcription factor binding,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 6-7 2004Mark A. Rainey Abstract Extracellular-regulated protein kinase 2 (ERK2) is a serine/threonine-specific protein kinase capable of phosphorylating multiple protein substrates within a cell. In an attempt to identify novel peptides that bind and inhibit the function of an active form of ERK2, phage display was carried out using a disulfide-constrained peptide library (X2CX14CX2). Several phage clones were identified by an enzyme-linked immunosorbent assay (ELISA) that competed with both a protein substrate and adenosine triphosphate (ATP) for immobilized ERK2. A chemically synthesized peptide derived from these experiments, NH2 -KKKIRCIRGWTKDIRTLADSCQY-COOH, inhibited ERK2 phosphorylation of the protein substrate Ets,138, exhibiting competitive and mixed inhibition towards Ets,138 and MgATP2,, respectively. Surprisingly, the same peptide displayed equally potent inhibition towards the phosphorylation of ATF2 by p38 MAPK,, another MAP kinase that has ,46% sequence similarity to ERK2. This study indicates that active ERK2 can be targeted by phage display to find novel antagonists to kinase function and suggests that protein-binding sites within the MAPK family may contain conserved features that render them susceptible to ligand binding. Copyright © 2004 John Wiley & Sons, Ltd. [source] MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cellsFEBS JOURNAL, Issue 22 2009Pedro M. Borralho MicroRNAs are aberrantly expressed in cancer; microRNA-143 (miR-143) is down-regulated in colon cancer. HCT116 human colorectal cancer cells were used to investigate the biological role of miR-143. Transient miR-143 overexpression resulted in an approximate 60% reduction in cell viability. In addition, stable miR-143 overexpressing cells were selected with G418 and exposed to 5-fluorouracil. Increased stable expression of miR-143 was associated with decreased viability and increased cell death after exposure to 5-fluorouracil. These changes were associated with increased nuclear fragmentation and caspase -3, -8 and -9 activities. In addition, extracellular-regulated protein kinase 5, nuclear factor-,B and Bcl-2 protein expression was down-regulated by miR-143, and further reduced by exposure to 5-fluorouracil. In conclusion, miR-143 modulates the expression of key proteins involved in the regulation of cell proliferation, death and chemotherapy response. In addition, miR-143 increases the sensitivity of colon cancer cells to 5-fluorouracil, probably acting through extracellular-regulated protein kinase 5/nuclear factor-,B regulated pathways. Collectively, the data obtained in the present study suggest anti-proliferative, chemosensitizer and putative pro-apoptotic roles for miR-143 in colon cancer. [source] ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entryGENES, CHROMOSOMES AND CANCER, Issue 2 2009Keika Zen Using high-density oligonucleotide microarrays, we investigated DNA copy-number aberrations in cell lines derived from hepatocellular carcinomas (HCCs) and detected a novel amplification at 17p11. To identify the target of amplification at 17p11, we defined the extent of the amplicon and examined HCC cell lines for expression of all seven genes in the 750-kb commonly amplified region. Mitogen-activated protein kinase (MAPK) 7, which encodes extracellular-regulated protein kinase (ERK) 5, was overexpressed in cell lines in which the gene was amplified. An increase in MAPK7 copy number was detected in 35 of 66 primary HCC tumors. Downregulation of MAPK7 by small interfering RNA suppressed the growth of SNU449 cells, the HCC cell line with the greatest amplification and overexpression of MAPK7. ERK5, phosphorylated during the G2/M phases of the cell cycle, regulated entry into mitosis in SNU449 cells. In conclusion, our results suggest that MAPK7 is likely the target of 17p11 amplification and that the ERK5 protein product of MAPK7 promotes the growth of HCC cells by regulating mitotic entry. © 2008 Wiley-Liss, Inc. [source] Angiotensin II promotes the phosphorylation of cyclic AMP-responsive element binding protein (CREB) at Ser133 through an ERK1/2-dependent mechanismJOURNAL OF NEUROCHEMISTRY, Issue 6 2001Martín Cammarota In cells from the adrenal medulla, angiotensin II (AII) regulates both the activity and mRNA levels of catecholamine biosynthetic enzymes whose expression is thought to be under the control of cAMP-responsive element (CRE) binding protein (CREB). In this study, we evaluated the effect of AII stimulation on CREB phosphorylation at Ser133 (pCREB) in bovine adrenal chromaffin cells (BACC). We found that AII produces a rapid and AII type-1 receptor (AT1)-dependent increase in pCREB levels, which is blocked by the MEK1/2 inhibitor U0126 but not by H-89, SB203580 or KN-93, suggesting that it is mediated by the extracellular-regulated protein kinases 1 and 2 (ERK1/2) and not by cAMP-dependent protein kinase (PKA), p38 mitogen-activated protein kinase (p38MAPK) or Ca2+/calmodulin-dependent protein kinases (CaMKs) dependent pathways. Gel-shift experiments showed that the increase in pCREB levels is accompanied by an ERK1/2-dependent upregulation of CRE-binding activity. We also found that AII promotes a rapid and reversible increase in the activity of the non-receptor tyrosine kinase Src and that the inhibition of this enzyme completely blocks the AII-induced phosphorylation of ERK1/2, the CREB kinase p90RSK and CREB. Our data support the hypothesis that in BACC, AII upregulates CREB functionality through a mechanism that requires Src-mediated activation of ERK 1/2 and p90RSK. [source] | ||||||||||