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A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development
Feng Zhang,Jingwen Yu,Tao Yang,Dan Xu,Zhixia Chi,Yanheng Xia and Zhiheng Xu
The Journal of Biological Chemistry
Abstract
Disturbance of neuronal migration may cause various neurological disorders. Both the transforming growth factor-β (TGF-β) signaling and microcephaly associated protein WDR62 are important for neuronal migration during brain development, however, the underlying molecular mechanisms involved remain unclear. We show here that knockout or knockdown of Tak1 (TGFβ-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical development and that the migration defects incurred by knockout and/or knockdown of Tβr2 (type II TGF-β receptor) or Tak1 can be partially rescued by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly associated protein WDR62 and the RAC1-interacting protein POSH (plenty of SH3's). Components of the complex coordinate with each other in the regulation of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes are involved in the diversified biological and pathological functions during brain development and pathogenesis of diseases.
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论文编号: |
DOI:10.1074/jbc.M116.716811 |
论文题目: |
A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development |
英文论文题目: |
A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development |
第一作者: |
Feng Zhang,Jingwen Yu,Tao Yang,Dan Xu,Zhixia Chi,Yanheng Xia and Zhiheng Xu |
英文第一作者: |
Feng Zhang,Jingwen Yu,Tao Yang,Dan Xu,Zhixia Chi,Yanheng Xia and Zhiheng Xu |
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2016-06-10 |
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摘要: |
Disturbance of neuronal migration may cause various neurological disorders. Both the transforming growth factor-β (TGF-β) signaling and microcephaly associated protein WDR62 are important for neuronal migration during brain development, however, the underlying molecular mechanisms involved remain unclear. We show here that knockout or knockdown of Tak1 (TGFβ-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical development and that the migration defects incurred by knockout and/or knockdown of Tβr2 (type II TGF-β receptor) or Tak1 can be partially rescued by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly associated protein WDR62 and the RAC1-interacting protein POSH (plenty of SH3's). Components of the complex coordinate with each other in the regulation of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes are involved in the diversified biological and pathological functions during brain development and pathogenesis of diseases. |
英文摘要: |
Disturbance of neuronal migration may cause various neurological disorders. Both the transforming growth factor-β (TGF-β) signaling and microcephaly associated protein WDR62 are important for neuronal migration during brain development, however, the underlying molecular mechanisms involved remain unclear. We show here that knockout or knockdown of Tak1 (TGFβ-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical development and that the migration defects incurred by knockout and/or knockdown of Tβr2 (type II TGF-β receptor) or Tak1 can be partially rescued by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly associated protein WDR62 and the RAC1-interacting protein POSH (plenty of SH3's). Components of the complex coordinate with each other in the regulation of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes are involved in the diversified biological and pathological functions during brain development and pathogenesis of diseases. |
刊物名称: |
The Journal of Biological Chemistry |
英文刊物名称: |
The Journal of Biological Chemistry |
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Feng Zhang,Jingwen Yu,Tao Yang,Dan Xu,Zhixia Chi,Yanheng Xia and Zhiheng Xu. A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development. The Journal of Biological Chemistry. DOI:10.1074/jbc.M116.716811 |
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