Persistent Activation of c-Jun N-terminal Kinase 1 (JNK1) in Radiation-induced Apoptosis

doi:10.1074/jbc.271.2.631

Persistent Activation of c-Jun N-terminal Kinase 1 (JNK1) in Radiation-induced Apoptosis (*)

From the Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030

^¶ To whom correspondence should be addressed:
Dept. of Microbiology and Immunology, M929, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
Tel.: 713-798-4665; Fax: 713-798-3700.

Abstract

The c-Jun N-terminal kinases (JNK) are activated by various stimuli, including UV light, interleukin-1, tumor necrosis factor-α (TNF-α), and CD28 costimulation. Induction of JNK by TNF-α, a strong apoptosis inducer, implies a possible role of JNK in the regulation of programmed cell death. Present studies show that lethal doses of radiation (GR) induced JNK activities at the early phase of apoptosis in Jurkat T-cells. We demonstrate that JNK1 was activated by either the T-cell activation signals, anti-CD28 monoclonal antibody plus phorbol 12-myristate 13-acetate (PMA), or the apoptosis-inducing treatment, GR; however, the induction patterns were different. In contrast to the rapid and transient JNK1 activation caused by CD28 signaling plus PMA, GR induced a delayed and persistent JNK1 activation. This implies a distinct regulatory mechanism and specific function of JNK1 in irradiated cells. The nuclear and cytosolic JNK1 activities were simultaneously increased in the irradiated cells without an evident change in the protein levels. The abilities of GR to induce JNK1 activation and DNA fragmentation were correlated. Peripheral blood lymphocytes were more sensitive to GR than Jurkat cells in JNK1 induction. The responsiveness of JNK1 to GR suggests the involvement of JNK1 in the initiation of the apoptosis process.

Footnotes

↵^§ Supported by National Institutes of Health Predoctoral Fellowship in AIDS Research T32-AI7483.
↵* This work was supported by National Institutes of Health Grants R01-GM49875 and R01-AI38649 (to T.-H. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

GR

radiation

JNK

c-Jun N-terminal kinase

GST

glutathione S-transferase

PMA

phorbol 12-myristate 13-acetate

MAP kinase

mitogen-activated protein kinase

MAPK

MAP kinase

ERK

extracellular signal-regulated kinase

mAb

monoclonal antibody

Gy

gray

Ab

antibody

Mops

4-morpholinepropanesulfonic acid

PAGE

polyacrylamide gel electrophoresis.
- Received October 10, 1995.