title: The activation of ERK1/2 via a tyrosine kinase pathway attenuates trail-induced apoptosis in HeLa cells.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves as an extracellular signal that triggers apoptosis in tumor cells. To characterize the molecular events involved in TRAIL-induced apoptotic signaling, we investigated the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in HeLa cell death. Here we show that TRAIL-activated ERK1/2 through a tyrosine kinase-dependent pathway, subsequently elevated anti-apoptotic Bcl-2 protein levels. ERK1/2 inhibition with PD98059 promoted apoptotic cell death through the downregulation of ERK1/2 activity and Bcl-2 protein levels. Moreover, tyrosine kinase inhibition with Genistein in TRAIL-induced apoptosis effectively attenuated ERK1/2 activity and enhanced apoptotic cell death. Taken together, our results indicate that ERK1/2 activation via tyrosine kinase pathway plays a protective role as the cellular defense mechanism through the upregulation of Bcl-2 protein levels in TRAIL-induced apoptosis.
authors.affiliation: Department of Anatomy, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Myoung Woo
authors.initials: MW
authors.lastname: Lee
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Bach
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Do Yeon
authors.initials: DY
authors.lastname: Lee
authors.forename: Wan Seok
authors.initials: WS
authors.lastname: Joo
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Soon Cheol
authors.initials: SC
authors.lastname: Park
authors.forename: Kyung Yong
authors.initials: KY
authors.lastname: Kim
authors.forename: Won Bok
authors.initials: WB
authors.lastname: Lee
authors.forename: Sung Su
authors.initials: SS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D015536:Down-Regulation; D004789:Enzyme Activation; D019254:Genes, bcl-2; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D048052:Mitogen-Activated Protein Kinase 3