Identification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1
Identification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1
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DOI：
10.1159/000015219
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Tokino, T
中科院分区：
文献类型：
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作者：
Oda, K;Shiratsuchi, T;Tokino, T
BAI1 （brain-specific angiogenesis inhibitor 1）最初是作为p53靶基因在脑内特异性表达而分离出来的。为了阐明其功能，我们一直在寻找与BAI1细胞质结构域相关的细胞蛋白。以其胞内羧基末端为“诱饵”，在酵母双杂交系统中分离得到一个cDNA克隆BAIAP2，其核苷酸序列编码一个521个氨基酸的蛋白，与鼠胰岛素受体激酶的58/53 kda底物具有显著的同源性。由于Northern blot检测的BAIAP2表达谱与BAI 1几乎相同，BAIAP2似乎主要在神经元中活跃。体外结合实验证实，BAI1富含脯氨酸的细胞质片段与BAIAP2的Src同源3 （SH3）结构域相互作用。双色免疫荧光分析显示，在COS-7细胞中，BAIAP2与BAI1共表达时定位于细胞质膜；与BAI1无关的BAIAP2在细胞质中呈弥漫性分布。BAI1蛋白主要定位于生长锥富集的亚细胞部分，表明BAI1可能是一种诱导生长锥的细胞粘附分子。作为BAI1的蛋白伙伴，BAIAP2可能是神经元生长过程中连接膜和细胞骨架的重要环节。
BAI1 (brain-specific angiogenesis inhibitor 1) was originally isolated as a p53-target gene specifically expressed in brain. To clarify its function, we have been searching for cellular proteins that associate with the cytoplasmic domain of BAI1. Using its intracellular carboxyl terminus as "bait" in a yeast two-hybrid system, we isolated a cDNA clone named BAIAP2 whose nucleotide sequence would encode a 521-amino acid protein showing significant homology to a 58/53-kDa substrate of insulin-receptor kinase in the hamster. As the expression profile of BAIAP2 examined by Northern blot analysis was almost identical to that of BAI 1, BAIAP2 appears to be active mainly in neurons. In vitro binding assays confirmed that a proline-rich cytoplasmic fragment of BAI1 interacted with the Src homology 3 (SH3) domain of BAIAP2. Double-color immunofluorescent analysis revealed that BAIAP2 was localized at the cytoplasmic membrane when it was coexpressed with BAI1 in COS-7 cells; BAIAP2 not associated with BAI1 was diffused in the cytoplasm. Predominant localization of BAI1 protein in a sub-cellular fraction enriched in growth cones indicated a possible role of BAI1 as a cell adhesion molecule inducing growth cone guidance. As a protein partner of BAI1, BAIAP2 may represent an important link between membrane and cytoskeleton in the process of neuronal growth.