Korean J Phys Anthropol.  2004 Sep;17(3):187-196.

The Activation of ERK1/2 Via Tyrosine Kinase Pathway Attenuates TRAIL-induced Apoptosis in HeLa cell

• Noh YH
• Lee MW
• Kim DS
• Lee DY
• Kim SW
• Kang YK
• Sohn DS
• Park SC
• Chung YH
• Kim KY
• Kim SS
• Lee WB

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves as an extracellular signal triggering 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 the apoptosis using HeLa cells. Here we show that TRAIL pronounced ERK1/2 activation through a tyrosine kinase-dependent mechanism, subsequently elevated anti-apoptotic Bcl-2 protein levels. Pretreatment with Genistein, an inhibitor of tyrosine kinase, significantly attenuated ERK1/2 activation and enhanced cell death. Moreover, inhibition of ERK1/2 with PD98059 promoted apoptotic cell death through the down-regulation of ERK1/2 activity and Bcl-2 protein levels. Taken together, our results suggest that the activation of ERK1/2 via tyrosine kinase pathway plays a protective role as the mechanism of cellular defense through the up-regulation of Bcl-2 protein levels in TRAIL-induced apoptosis.

Keyword

TRAIL; ERK1/2; Tyrosine kinase; Bcl-2 protein; Apoptosis

MeSH Terms

Apoptosis*
Cell Death
Down-Regulation
Genistein
HeLa Cells*
Humans
Necrosis
Phosphotransferases
Protein-Tyrosine Kinases*
Tyrosine*
Up-Regulation
Genistein
Phosphotransferases
Protein-Tyrosine Kinases
Tyrosine