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Activin receptor-like kinase-7 induces apoptosis through activation of MAPKs in a Smad3-dependent mechanism in hepatoma cells.

DC Field Value Language
dc.contributor.authorKim, BC-
dc.contributor.authorvan Gelder, H-
dc.contributor.authorKim, TA-
dc.contributor.authorLee, HJ-
dc.contributor.authorBaik, KG-
dc.contributor.authorChun, HH-
dc.contributor.authorLee, DA-
dc.contributor.authorChoi, KS-
dc.contributor.authorKim, SJ-
dc.date.accessioned2011-07-15T01:18:34Z-
dc.date.available2011-07-15T01:18:34Z-
dc.date.issued2004-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/3359-
dc.description.abstractActivin receptor-like kinase (ALK)7 is a type I serine/threonine kinase receptor of the transforming growth factor (TGF)-beta family of proteins that has similar properties to other type I receptors when activated. To see whether ALK7 can induce apoptosis as can some of the other ALK proteins, we infected the FaO rat hepatoma cell line with adenovirus expressing a constitutively active form of the ALK7. Cells infected with active ALK7 adenovirus showed an apoptotic-positive phenotype, as opposed to those that were infected with a control protein. DNA fragmentation assays and fluorescence-activated cell sorter analysis also indicated that ALK7 infection induced apoptosis in FaO cells. We also confirmed this finding in Hep3B human hepatoma cells by transiently transfecting the constitutively active form of ALK7, ALK7(T194D). Investigation into the downstream targets and mechanisms involved in ALK7-induced apoptosis revealed that the TGF-beta signaling intermediates, Smad2 and -3, were activated, as well as the MAPKs JNK and p38. In addition, caspase-3 and -9 were also activated, and cytochrome c release from the mitochondria was observed. Short interfering RNA-mediated inhibition of Smad3 markedly suppressed ALK7-induced caspase-3 activation. Treatment with protein synthesis inhibitors or the expression of the dominant-negative form of the stress-activated protein/extracellular signal-regulated kinase 1 abolished not only JNK activation but apoptosis as well. Taken together, these results suggest that ALK7 induces apoptosis through activation of the traditional TGF-beta pathway components, thus resulting in new gene transcription and JNK and p38 activation that initiates cross-talk with the cellular stress death pathway and ultimately leads to apoptosis.-
dc.language.isoen-
dc.subject.MESHActivin Receptors, Type I/*metabolism-
dc.subject.MESHAdenoviridae/genetics/metabolism-
dc.subject.MESHAnimals-
dc.subject.MESH*Apoptosis-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCarcinoma, Hepatocellular/metabolism/*pathology-
dc.subject.MESHCaspase 3-
dc.subject.MESHCaspase 9-
dc.subject.MESHCaspases/metabolism-
dc.subject.MESHCell Line-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Separation-
dc.subject.MESHCell Survival-
dc.subject.MESHCytochromes c/metabolism-
dc.subject.MESHDNA Fragmentation-
dc.subject.MESHDNA-Binding Proteins/*metabolism-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHFlow Cytometry-
dc.subject.MESHGenes, Dominant-
dc.subject.MESHGenetic Vectors-
dc.subject.MESHHumans-
dc.subject.MESH*MAP Kinase Signaling System-
dc.subject.MESHMitogen-Activated Protein Kinases/metabolism-
dc.subject.MESHPlasmids/metabolism-
dc.subject.MESHRNA, Small Interfering/metabolism-
dc.subject.MESHRats-
dc.subject.MESHSmad2 Protein-
dc.subject.MESHSmad3 Protein-
dc.subject.MESHTrans-Activators/*metabolism-
dc.subject.MESHTransfection-
dc.subject.MESHTransforming Growth Factor beta/metabolism-
dc.subject.MESHTransforming Growth Factor beta1-
dc.subject.MESHp38 Mitogen-Activated Protein Kinases-
dc.titleActivin receptor-like kinase-7 induces apoptosis through activation of MAPKs in a Smad3-dependent mechanism in hepatoma cells.-
dc.typeArticle-
dc.identifier.pmid15107418-
dc.identifier.urlhttp://www.jbc.org/cgi/pmidlookup?view=long&pmid=15107418-
dc.contributor.affiliatedAuthor최, 경숙-
dc.type.localJournal Papers-
dc.identifier.doi10.1074/jbc.M313277200-
dc.citation.titleThe Journal of biological chemistry-
dc.citation.volume279-
dc.citation.number27-
dc.citation.date2004-
dc.citation.startPage28458-
dc.citation.endPage28465-
dc.identifier.bibliographicCitationThe Journal of biological chemistry, 279(27):28458-28465, 2004-
dc.identifier.eissn1083-351X-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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