Exp Cell Res. 2003 Sep 10;289(1):67-76.

Lyn regulates the cell death response to ultraviolet radiation through c-Jun N terminal kinase-dependent Fas ligand activation.

Shangary S, Lerner EC, Zhan Q, Corey SJ, Smithgall TE, Baskaran R.

Source

Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Abstract

The Src-related tyrosine kinase, Lyn, plays an important role in mediating the cell cycle arrest and cell death response to genotoxic agents such as ionizing radiation. In this report we provide evidence to show that the catalytic function of Lyn is required for ultraviolet radiation (UV)- and methyl methanesulfonate (MMS)- but not for cisplatin (CDDP)- or ionizing radiation (IR)-induced cell death. Consequently, fibroblasts deficient in Lyn function were protected against cell death induction by UV and MMS, but showed normal cell death to IR and CDDP treatment. In Lyn(-/-) cells, UV-induced activation of stress-responsive kinases, Erk1/2 and p38, was normal; however, JNK activation was diminished. In addition, FasL induction by UV was also diminished in these cells. Reintroduction of wild-type Lyn restored JNK activation, FasL induction, and sensitivity to UV and MMS. A role for FasL in the cell death induction by Lyn-JNK signaling is indicated by the inhibition of cell death response by FasL neutralizing antibody. Together, the results support the presence of the Lyn-JNK signaling pathway that mediates the cell death response to UV and MMS treatment through FasL induction.

PMID:: 12941605; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

Research Support, U.S. Gov't, P.H.S.

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Medical

FAS Gene - Genetics Home Reference

Molecular Biology Databases

Supplemental Content

Related citations

Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells. [J Biol Chem. 2003]
Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells.
Mansouri A, Ridgway LD, Korapati AL, Zhang Q, Tian L, Wang Y, Siddik ZH, Mills GB, Claret FX. J Biol Chem. 2003 May 23; 278(21):19245-56. Epub 2003 Mar 12.
The level of intracellular glutathione is a key regulator for the induction of stress-activated signal transduction pathways including Jun N-terminal protein kinases and p38 kinase by alkylating agents. [Mol Cell Biol. 1997]
The level of intracellular glutathione is a key regulator for the induction of stress-activated signal transduction pathways including Jun N-terminal protein kinases and p38 kinase by alkylating agents.
Wilhelm D, Bender K, Knebel A, Angel P. Mol Cell Biol. 1997 Aug; 17(8):4792-800.
The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in Jurkat cells by up-regulating Fas ligand expression. [J Immunol. 1998]
The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in Jurkat cells by up-regulating Fas ligand expression.
Faris M, Kokot N, Latinis K, Kasibhatla S, Green DR, Koretzky GA, Nel A. J Immunol. 1998 Jan 1; 160(1):134-44.
Opposing roles of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in the cellular response to ionizing radiation in human cervical cancer cells. [Mol Cancer Res. 2008]
Opposing roles of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in the cellular response to ionizing radiation in human cervical cancer cells.
Kim MJ, Choi SY, Park IC, Hwang SG, Kim C, Choi YH, Kim H, Lee KH, Lee SJ. Mol Cancer Res. 2008 Nov; 6(11):1718-31.
Long-term activation of SAPK/JNK, p38 kinase and fas-L expression by cisplatin is attenuated in human carcinoma cells that acquired drug resistance. [Int J Cancer. 2004]
Long-term activation of SAPK/JNK, p38 kinase and fas-L expression by cisplatin is attenuated in human carcinoma cells that acquired drug resistance.
Brozovic A, Fritz G, Christmann M, Zisowsky J, Jaehde U, Osmak M, Kaina B. Int J Cancer. 2004 Dec 20; 112(6):974-85.

See reviews... See all...

Cited by 3 PubMed Central articles

An overview of caspase: Apoptotic protein for silicosis. [Indian J Occup Environ Med. 2010]
An overview of caspase: Apoptotic protein for silicosis.
Tumane RG, Pingle SK, Jawade AA, Nath NN. Indian J Occup Environ Med. 2010 Aug; 14(2):31-8.
A RNA interference screen identifies the protein phosphatase 2A subunit PR55gamma as a stress-sensitive inhibitor of c-SRC. [PLoS Genet. 2007]
A RNA interference screen identifies the protein phosphatase 2A subunit PR55gamma as a stress-sensitive inhibitor of c-SRC.
Eichhorn PJ, Creyghton MP, Wilhelmsen K, van Dam H, Bernards R. PLoS Genet. 2007 Dec; 3(12):e218.
HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration. [Blood. 2007]
HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration.
Lu X, Chen J, Malumbres R, Cubedo Gil E, Helfman DM, Lossos IS. Blood. 2007 Dec 15; 110(13):4268-77. Epub 2007 Sep 6.

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Lyn regulates the cell death response to ultraviolet radiation through c-Jun N t...
Lyn regulates the cell death response to ultraviolet radiation through c-Jun N terminal kinase-dependent Fas ligand activation.
Exp Cell Res. 2003 Sep 10 ;289(1):67-76.

PubMed
Positional cloning of "Lisch-Like", a candidate modifier of susceptibility to ty...
Positional cloning of "Lisch-Like", a candidate modifier of susceptibility to type 2 diabetes in mice.
PLoS Genet. 2008 Jul 25 ;4(7):e1000137.

PubMed
Catabolism of caffeine in plants and microorganisms.
Catabolism of caffeine in plants and microorganisms.
Front Biosci. 2004 May 1 ;9:1348-59.

PubMed
Polypoid cystitis resulting from ovarian abscess.
Polypoid cystitis resulting from ovarian abscess.
Int Urogynecol J Pelvic Floor Dysfunct. 2007 May ;18(5):579-82. Epub 2006 Jul 15 .

PubMed
Detection, imputation, and association analysis of small deletions and null alle...
Detection, imputation, and association analysis of small deletions and null alleles on oligonucleotide arrays.
Am J Hum Genet. 2008 Jun ;82(6):1316-33.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Display Settings:

Send to: