Characterization of a novel ligand for Receptor Tyrosine Kinase ErbB

受体酪氨酸激酶 ErbB 的新型配体的表征

• 批准号: 09680620
• 负责人: HIGASHIYAMA Shigeki
• 金额: $ 2.56万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680620/
• 关键词: ErbB tyrosine kinase; Cell growth; Cell differentiation; neuregulin; NTAK; ErbB チロシンキナーゼ; EGF ファミリー; Neuregulin

A novel member of the epidermal growth factor (EGF) family, the neural- and thymus-derived activator for ErbB kinases (NTAK), has been purified and cloned.Five alternative spliced isoforms (alpha1, alpha 2 a alpha2b, beta, gamma) have been detected in the rat adrenal pheochromocytoma cell line, PC-12 cells.The rat NTAKalpha2a isoform exhibits 94% identity in its primary sequence with the human NTAKalpha isoform.In vivo, NTAK is only expressed in the brain of rat E11.5 embryos, and in the brain and thymus of adult rats.The soluble 46 kDa form binds directly to ErbB3 and B4, but not to ErbB1 or B2.NTA,K except gamma-isofrom, however, transactivates ErbB1 and B2 via heterodimerization with ErbB3 or B4.NTAK stimulates the differentiation of MDA-MB--453 cells and competitively inhibits the binding of 125I-neuregulin to these cells.In addition to these neuregulin-like properties, NTAK exhibits limited structural homology to neuregulins in the immunoglobulin (Ig)-like, EGF-like and hydrophobic domains.Thus, NTAK appears to be a new member of the EGF family displaying neuregulin properties.

已经纯化并克隆了表皮生长因子（EGF）家族的新成员，即ERBB激酶（NTAK）的神经和胸腺衍生的活化剂（NTAK）。在大鼠肾上腺嗜铬细胞瘤细胞系中已检测到PC-12细胞。大鼠ntakalpha2a同工型在其主要序列中与人Ntakalpha同型在其主要序列中表现出94％的身份。 ，在成年大鼠的大脑和胸腺中。可溶的46 kDa形式直接与Erbb3和b4结合，但不与ERBB1或B2.NTA，K，k除了gamma-isofrom，但是，通过ERBB3或B4或B4杂二聚化对ERBB1和B2进行反式激活。 ，EGF样和疏水结构域。因此，NTAK似乎是显示神经教特性的EGF家族的新成员。

项目成果

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Yokosaki, Y., Matsuura, N., Higashiyama, S., Murakami I., Obara, M., Yamakido, M., Shigeto, N., Chen, J., Sheppard, D.: "Identification of the ligand binding site for the integrin alpha9beta1 in the third fibronectin type III repeat of tenascin-C." J.Biol

Yokosaki, Y.、Matsuura, N.、Higashiyama, S.、Murakami I.、Obara, M.、Yamakido, M.、Shigeto, N.、Chen, J.、Sheppard, D.：“配体结合的鉴定

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