11 227

Cited 50 times in

Role of MAP kinases and their cross-talk in TGF-beta1-induced apoptosis in FaO rat hepatoma cell line.

Park, HJ; Kim, BC; Kim, SJ; Choi, KS
Hepatology (Baltimore, Md.), 35(6):1360-1371, 2002
Journal Title
Hepatology (Baltimore, Md.)
Transforming growth factor (TGF) beta1 is a potent inducer of apoptosis in the liver. During TGF-beta1-induced apoptosis, 3 mitogen-activated protein (MAP) kinases (extracellular signal-regulated kinase [ERK], c-Jun N-terminal kinase [JNK], and p38 kinase) showed simultaneously sustained activation in FaO rat hepatoma cells. TGF-beta1-induced apoptosis was markedly enhanced when ERK activation was selectively inhibited by the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD98059. In contrast, both interfering with p38 activity by overexpression of the dominant negative (DN) MKK6 mutant and inhibition of the JNK pathway by overexpression of the DN SEK1 mutant resulted in suppression of mitochondrial cytochrome c release, abrogating TGF-beta1-induced apoptosis. In addition, antiapoptotic Bcl-2 blocked mitochondrial cytochrome c release, suppressing TGF-beta1-induced activation of JNK and p38. Inhibition of ERK activity enhanced TGF-beta1-induced p38 and JNK activation. However, inhibition of the JNK pathway suppressed p38 but induced transient ERK activation. Similarly, interfering with the p38 pathway also attenuated JNK activation but generated transient ERK activation in response to TGF-beta1. These results indicate that disrupting one MAP kinase pathway affects the TGF-beta1-induced activation of other MAP kinases, suggesting cross-talk among MAP kinase pathways. In conclusion, we propose that the balance and integration of MAP kinase signaling may regulate commitment to TGF-beta1-induced apoptosis modulating the release of cytochrome c from mitochondria.
MeSH terms
AnimalsApoptosis/drug effects/*physiology*Carcinoma, HepatocellularCytochrome c Group/metabolismGene Expression/physiology*JNK Mitogen-Activated Protein Kinases*Liver NeoplasmsMAP Kinase Kinase 4MAP Kinase Signaling System/*physiologyMitochondria/metabolismMitogen-Activated Protein Kinase Kinases/metabolismMitogen-Activated Protein Kinases/metabolismProto-Oncogene Proteins c-bcl-2/geneticsRatsReceptor Cross-Talk/*physiologyTransforming Growth Factor beta/*pharmacologyTransforming Growth Factor beta1Tumor Cells, Culturedp38 Mitogen-Activated Protein Kinases
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
최, 경숙
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.