title: A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development.
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 knock-out 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 knock-out 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 Src homology). 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.
authors.affiliation: From the State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, the University of Chinese Academy of Sciences, Beijing 100101, and.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: From the State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Yu
authors.affiliation: From the State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: From the State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: From the State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101.
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Chi
authors.affiliation: From the State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, the University of Chinese Academy of Sciences, Beijing 100101, and.
authors.forename: Yanheng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: From the State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, the Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, the Parkinson's Disease Center, Beijing Institute for Brain Disorders, Beijing 100101, China zhxu@genetics.ac.cn.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020830:rac1 GTP-Binding Protein; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D020830:rac1 GTP-Binding Protein; D000099151:MAP Kinase Kinase Kinase 7
keywords: JNK; Rac (Rac GTPase); Wdr62; complex; migration; neuron; signal transduction; tak1; tgf-signaling