ABL-INTERACTOR-1, A NOVEL SH3 PROTEIN-BINDING TO THE CARBOXY-TERMINAL PORTION OF THE ABL PROTEIN, SUPPRESSES V-ABL TRANSFORMING ACTIVITY

ABL-INTERACTOR-1, A NOVEL SH3 PROTEIN-BINDING TO THE CARBOXY-TERMINAL PORTION OF THE ABL PROTEIN, SUPPRESSES V-ABL TRANSFORMING ACTIVITY
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DOI:
10.1101/gad.9.21.2583
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发表时间:
1995-11-01
影响因子:
10.5
通讯作者:
GOFF, SP
GOFF, SP
中科院分区:
生物学1区
文献类型:
--
作者:
SHI, YG;ALIN, K;GOFF, SP

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在小鼠白血病细胞系中发现了一种新的细胞蛋白Ab 1-interactor-1(Abi-1),它与Ab 1癌蛋白的羧基端区域特异性相互作用。该蛋白表现出同源异型基因的序列相似性,含有几个聚脯氨酸延伸,并包括一个src同源性3(SH 3)结构域在其羧基末端,这是需要结合到Abl蛋白。abi-l基因已经定位于小鼠2号染色体,并且在遗传上与c-abl基因座紧密连锁。该基因在小鼠中广泛表达,在骨髓、脾、脑和睾丸中发现最高水平的mRNA。Abi-1蛋白与v-Abl共免疫沉淀,并作为激酶活性的底物。当在NLH-3 T3细胞中过表达时,abi-1有效抑制表达全长p160(v-ab 1)激酶的Abelson白血病病毒的转化活性,但不影响表达截短的p90(v-ab 1)或v-src激酶的病毒的转化活性。我们认为Abi-1蛋白可能在转化或信号转导中作为Abl功能的调节剂。
A novel cellular protein, Ab1-interactor-1 (Abi-1), which specifically interacts with the carboxy-terminal region of Abl oncoproteins, has been identified in a mouse leukemia cell line. The protein exhibits sequence similarity to homeotic genes, contains several polyproline stretches, and includes a src homology 3 (SH3) domain at its very carboxyl terminus that is required for binding to Abl proteins. The abi-l gene has been mapped to mouse chromosome 2 and is genetically closely linked to the c-abl locus. The gene is widely expressed in the mouse, with highest levels of mRNA found in the bone marrow, spleen, brain, and testes. The Abi-l protein coimmunoprecipitates with v-Abl and serves as a substrate for kinase activity. When overexpressed in NLH-3T3 cells, abi-1 potently suppresses the transforming activity of Abelson leukemia virus expressing the full-length p160(v-ab1) kinase but does not affect the transforming activity of viruses expressing a truncated p90(v-ab1) or v-src kinases. We suggest that the Abi-l protein may serve as a regulator of Abl function in transformation or in signal transduction.