生物
海马结构
细胞生物学
免疫受体酪氨酸激活基序
信号转导
细胞因子
造血
胚胎干细胞
酪氨酸激酶
分子生物学
免疫学
干细胞
神经科学
遗传学
基因
SH2域
作者
Mitsuhiro Yamada,Toshikazu Takeshita,Shigeto Miura,Kazuko Murata,Yutaka Kimura,Naoto Ishii,Masato Nose,Hiroyuki Sakagami,Hisatake Kondo,Fumi Tashiro,Jun‐ichi Miyazaki,Hidetada Sasaki,Kazuo Sugamura
标识
DOI:10.1128/mcb.21.11.3807-3819.2001
摘要
STAM1, a member of the STAM (signal transducing adapter molecule) family, has a unique structure containing a Src homology 3 domain and ITAM (immunoreceptor tyrosine-based activation motif). STAM1 was previously shown to be associated with the Jak2 and Jak3 tyrosine kinases and to be involved in the regulation of intracellular signal transduction mediated by interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. Here we generated mice lacking STAM1 by using homologous recombination with embryonic stem cells. STAM1−/− mice were morphologically indistinguishable from their littermates at birth. However, growth retardation in the third week after birth was observed for the STAM1−/− mice. Unexpectedly, despite the absence of STAM1, hematopoietic cells, including T- and B-lymphocyte and other hematopoietic cell populations, developed normally and responded well to several cytokines, including IL-2 and GM-CSF. However, histological analyses revealed the disappearance of hippocampal CA3 pyramidal neurons in STAM1−/− mice. Furthermore, we observed that primary hippocampal neurons derived from STAM1−/− mice are vulnerable to cell death induced by excitotoxic amino acids or an NO donor. These data suggest that STAM1 is dispensable for cytokine-mediated signaling in lymphocytes but may be involved in the survival of hippocampal CA3 pyramidal neurons.
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