cAMP response element-binding protein (CREB) is required for epidermal growth factor (EGF)-induced cell proliferation and serum response element activation in neural stem cells isolated from the forebrain subventricular zone of adult mice

DOI Web Site 被引用文献3件 参考文献71件
  • Iguchi Hironobu
    Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan
  • Mitsui Tetsuo
    Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan
  • Ishida Maho
    Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan
  • Kanba Shigenobu
    Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  • Arita Jun
    Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan

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抄録

Neurogenesis, which occurs not only in the developing brain but also in restricted regions in the adult brain including the forebrain subventricular zone (SVZ), is regulated by a variety of environmental factors, extracellular signals, and intracellular signal transduction pathways. We investigated whether the transcription factor cAMP response element (CRE)-binding protein (CREB) is involved in the regulation of cell proliferation of neural stem cells (NSCs) isolated from the SVZ of adult mice. Treatment of NSCs with the protein kinase A (PKA) inhibitors H89 and KT5720 inhibited epidermal growth factor (EGF)-stimulated NSC proliferation. Similar inhibition was observed when a dominant-negative mutant of CREB (MCREB) was expressed. EGF treatment increased CRE-mediated transcriptional activity, but this increase was much less than that caused by treatment with the adenylate cyclase activator forskolin, which changed neither basal nor EGF-stimulated proliferation of NSCs. Neither PKA inhibitors nor MCREB expression blocked EGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), a protein kinase mediating EGF’s mitogenic action. However, MCREB suppressed EGF-induced expression of several immediately early genes including c-fos, c-jun, jun-B, and fra-1 and subsequent AP-1 transcriptional activation. MCREB expression also inhibited the ability of EGF to stimulate transcriptional activation mediated by the serum response element (SRE), a promoter sequence regulating c-fos gene expression. These results suggest that basal activity of CREB is required for the mitogenic signaling of EGF in NSCs at a level between ERK activation and SRE-mediated transcriptional activation.

収録刊行物

  • Endocrine Journal

    Endocrine Journal 58 (9), 747-759, 2011

    一般社団法人 日本内分泌学会

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