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Molecular Cloning of Multiple Splicing Variants of JIP-1 Preferentially Expressed in Brain
- Source :
- Journal of Neurochemistry. 72:1335-1343
- Publication Year :
- 2001
- Publisher :
- Wiley, 2001.
-
Abstract
- Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) is activated by a variety of cellular or environmental stresses. Proper regulation of the SAPK/JNK pathway may be critical for cell survival or death under various conditions. In this study, we report the molecular cloning of novel isoforms of JIP-1, which harbor a putative phosphotyrosine interaction domain and a helix-loop-helix domain, as well as an SH3 homologous region in the C terminus. Northern analysis indicates that transcription variant jip-1 is expressed in brain and kidney and transcription variants jip-2 and jip-3 are specifically expressed in brain. In situ hybridization data showed that the hybridized jip messages were heavily concentrated in adult brain, and were particularly enriched in the cerebral cortex and hippocampus, the brain regions vulnerable to pathological states such as hypoxia-ischemia, epilepsy, and Alzheimer’s disease. All the deduced protein products of the jip transcription variants appear to have a similar property in that they inhibit the SAPK/JNK stimulation when overexpressed. Inhibition of SAPK activation by overexpression of the novel isoform JIP-2a resulted in suppression of etoposide-induced cell death in a neuroglioma cell line, N18TG. These findings suggest that JIP may play an important role in regulation of the SAPK pathway that is involved in stress-induced cellular responses.
- Subjects :
- Gene isoform
Programmed cell death
DNA, Complementary
Transcription, Genetic
MAP Kinase Kinase 4
Molecular Sequence Data
Apoptosis
In situ hybridization
Molecular cloning
Biology
Biochemistry
Gene Expression Regulation, Enzymologic
Mice
Cellular and Molecular Neuroscience
Transcription (biology)
Animals
Cloning, Molecular
Protein kinase A
Adaptor Proteins, Signal Transducing
Gene Library
Brain Chemistry
Mitogen-Activated Protein Kinase Kinases
Neurons
Genetics
Mice, Inbred BALB C
Sequence Homology, Amino Acid
Kinase
JNK Mitogen-Activated Protein Kinases
Brain
Cell biology
Alternative Splicing
RNA splicing
Carrier Proteins
Protein Kinases
Signal Transduction
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 72
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi.dedup.....ecf340860b2a2fb2dd2e886c17a7a5cb