Identification of POSH2, a novel homologue of the c-Jun N-terminal kinase scaffold protein POSH.
The c-Jun N-terminal kinase (JNK) pathway plays an important role in neuronal apoptosis both during normal CNS development and following stroke in adult animals. As with other MAP kinase pathways, scaffold proteins regulate JNK signaling. The scaffold protein POSH (Plenty of SH3s) enhances JNK activation and apoptosis. We identified a POSH homologue, POSH2, which was cloned from rat brain and is present in cortical neurons in vitro. POSH2 mRNA is expressed in a variety of tissues including brain, and this distribution partially overlaps with that of POSH. POSH2 overexpression promotes JNK activation in HEK293 cells and promotes apoptosis in neuronal PC12 cells, which is blocked by a dominant-negative c-Jun. Finally POSH2 contains a functional RING domain and enhances the stability of coexpressed mixed-lineage kinases. These results indicate that POSH2 may regulate JNK activation and consequent apoptosis under conditions of increased expression.
Wilhelm
Michael
M
Department of Pediatrics, Columbia University Health Sciences, New York, NY 10032, USA. mw2025@columbia.edu
Kukekov
Nickolay V
NV
Xu
Zhiheng
Z
Greene
Lloyd A
LA
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D004795:Enzyme Stability / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D017434:Protein Structure, Tertiary / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger; C506024:Sh3rf1 protein, rat; C523251:Sh3rf2 protein, rat; D048031:JNK Mitogen-Activated Protein Kinases