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A new mechanism of receptor tyrosine signaling and its role in brain development

发布日期:2017-09-22    浏览次数:

北京大学神经科学研究所学术报告

A new mechanism of receptor tyrosine signaling and its role in brain development

 

 

报告人:Gabriel Corfas
Associate Chair, Department of Otolaryngology
Director, Kresge Hearing Research Institute
University of Michigan

 

报告摘要:

 

Receptor Tyrosine Kinases (RTKs) form a family of transmembrane signaling molecules that participate in many key cellular processes, including proliferation, survival, migration and differentiation. These receptors have long been thought to exert their biological effect through canonical RTK signaling. In this signaling modality, ligand binding induces receptor dimerization, resulting in RTK trans-phosphorylation that creates binding sites for adaptor proteins, which then mediate activation of downstream soluble kinases that go on to phosphorylate targets such as transcription factors, which then alter transcription of their specific target genes. Studying ErbB4, a receptor for neuregulin-1 (NRG1) and other trophic factors, we and others discovered a novel mechanism for RTK function involving direct nuclear signaling. In this alternate RTK pathway, ligand-induced activation of the ErbB4-JMa isoform induces cleavage of the receptor, first by the tumor necrosis factor-α-converting enzyme (TACE) in the extracellular juxtamembrane domain, then by γ-secretase within the transmembrane domain. The ligand-induced cleavage of ErbB4 depends on its kinase activity. This sequence of events results in the release of the activated soluble intracellular domain (E4ICD), which translocates to the nucleus via a nuclear localization sequence. In this presentation, I will discuss our findings on the roles of direct nuclear signaling by ErbB4 in neural stem cells in the embryonic cerebral cortex, and it implications for astrogenesis and genomic stability.

 

主持人:于常海教授
 间:2017927日(周三)15:45
 点:神科所会议室(北医中心楼一层北侧)