Alternative splicing variants of the human DBL (MCF-2) proto-oncogene
Alternative splicing variants of the human DBL (MCF-2) proto-oncogene
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DOI：
10.1016/s0006-291x(02)02645-1
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发表时间：
2002-12-06
影响因子：
3.1
通讯作者：
Shiozawa, S
中科院分区：
文献类型：
--
作者：
Komai, K;Okayama, R;Shiozawa, S
DBL（MCF-2）原癌基因是调节GTP酶的Rho家族的原型鸟嘌呤核苷酸交换因子（GEF）。在这篇文章中，我们描述了三种新的Dbl剪接变体的分离。原型Db 1基因（在此指定为var.1）含有25个外显子，而剪接变体2（var.2）缺少外显子23和24。var.3含有来自5 '-UTR的另外3个外显子代替外显子1，而var.4、var.2和var.3含有外显子10和11之间的48 bp插入，导致16个氨基酸的插入。我们发现，var.1只在大脑中表达，而var.3在心脏，肾脏，脾脏，肝脏和睾丸中表达，var.4在大脑，心脏，肾脏，睾丸，胎盘，胃和外周血中表达。Db 1蛋白在脑、心、肾、肠、肌肉、肺和睾丸中可检测到。对GEF活性的测定显示，var.2对Cdc 42表现出降低的GEF活性，var.3对Racl和Cdc 42表现出弱但显著的活性，var.4对RhoA和Cdc 42表现出显著的活性，而var.1对RhoA、Racl或Cdc 42不表现出活性。总之，我们描述了4种人DBL原癌基因的剪接变体，它们显示出不同的组织分布和GEF特异性。(C)2002 Elsevier Science（美国）。All rights reserved.
The DBL (MCF-2) proto-oncogene is a prototype guanine nucleotide exchange factor (GEF) that modulates the Rho family of GTPases. In this communication we describe the isolation of three novel splicing variants of Dbl. The prototype Dbl gene (designated var.1 here) contains 25 exons, while splicing variant 2 (var.2) lacks exons 23 and 24.Var.3 contains additional 3 exons from 5'-UTR in place of exon 1, while var.4, var.2, and var.3 contain a 48 bp insertion between exons 10 and 11, resulting in the insertion of 16 amino acids. We found that var.1 was expressed only in brain, whereas var.3 was expressed in heart, kidney, spleen, liver, and testis, and var.4 in brain, heart, kidney, testis, placenta, stomach, and peripheral blood. The Dbl protein was detectable in brain, heart, kidney, intestine, muscle, lung, and testis. An assay for GEF activity revealed that the var.2 exhibits decreased GEF activity towards Cdc42, var.3 exhibits a weak but significant activity toward Racl and Cdc42, var.4 exhibits significant activity toward RhoA and Cdc42, while var.1 exhibits no activity toward RhoA, Rac1, or Cdc42. In summary, we describe 4 splicing variants of the human DBL proto-oncogene that show different tissue distributions and GEF specificities. (C) 2002 Elsevier Science (USA). All rights reserved.