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Molecular Cloning of Multiple Splicing Variants of JIP‐1 Preferentially Expressed in Brain
Author(s) -
Kim InJung,
Lee KoWoon,
Park Byung Young,
Lee JaKyeong,
Park Jihyun,
Choi In Young,
Eom SooJung,
Chang TongShin,
Kim Myung Jin,
Yeom Young Il,
Chang Sung Key,
Lee YoungDon,
Choi EuiJu,
Han PyungLim
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.721335.x
Subject(s) - gene isoform , alternative splicing , biology , microbiology and biotechnology , rna splicing , transcription factor , transcription (linguistics) , neuroscience , gene , genetics , rna , linguistics , philosophy
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.