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Level of HgCl 2 ‐mediated phosphorylation of intracellular proteins determines death of thymic T‐lymphocytes with or without DNA fragmentation
Author(s) -
Akhand Anwarul A.,
Kato Masashi,
Suzuki Haruhiko,
Miyata Toshio,
Nakashima Izumi
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19981101)71:2<243::aid-jcb9>3.0.co;2-v
Subject(s) - staurosporine , phosphorylation , microbiology and biotechnology , protein kinase a , kinase , dna fragmentation , protein phosphorylation , biology , programmed cell death , mapk/erk pathway , fragmentation (computing) , mitogen activated protein kinase , biochemistry , apoptosis , ecology
Exposure to Hg 2+ at a wide range of concentrations (approximately 1–100 μM) more or less caused the death of murine thymic T‐lymphocytes, and exposure to 1 μM but not 10 μM (or more) of Hg 2+ induced DNA fragmentation. Exposure of cells to Hg 2+ caused phosphorylation of multiple cellular proteins at the tyrosine residue in a concentration‐dependent manner. We found that not only the DNA fragmentation induced by 1 μM Hg 2+ but also the cell death bypassing DNA fragmentation caused by 10 μM or more Hg 2+ was partly inhibited by protein kinase inhibitors such as staurosporine and herbimycin A. This result suggested the involvement of a protein phosphorylation‐linked signal in the mechanism of the Hg 2+ ‐mediated cell death with or without DNA fragmentation. Analysis of proteins by both one‐ and two‐dimensional electrophoresis and immunoblot showed that a 52‐kDa Shc protein was heavily phosphorylated by an early signal delivered by a high concentration of Hg 2+ , which also phosphorylated extracellular signal‐regulated kinase 1 (ERK1; p44) and ERK2 (p42) of the mitogen‐activated protein kinase (MAPK) family in a concentration‐ and time‐dependent manner. The c‐Jun amino terminal kinase (p54), which is a distant relative of the MAPK family, was also phosphorylated by the treatment with Hg 2+ . This eventually formed the signaling cascade that ended with a nuclear target by phosphorylating c‐jun at the serine 73. This phosphorylation of c‐jun was inhibited by staurosporine. These results suggest that a high level of Hg 2+ ‐mediated protein phosphorylation‐linked signal induces rapid cell death bypassing DNA fragmentation, whereas a lower level induces cell death accompanying DNA fragmentation. This conclusion in turn implies that DNA fragmentation is not always a prerequisite for the signal transduction‐dependent cell death of T‐lymphocytes. J. Cell. Biochem. 71:243–253, 1998. © 1998 Wiley‐Liss, Inc.