Major transcript variants of VAV3, a new member of the VAV family of guanine nucleotide exchange factors.

Major transcript variants of VAV3, a new member of the VAV family of guanine nucleotide exchange factors.
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VAV3 的主要转录变体,VAV 鸟嘌呤核苷酸交换因子家族的新成员。

DOI:
10.1016/s0378-1119(00)00026-3
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发表时间:
2000
期刊:
影响因子:
3.5
通讯作者:
Welsh,J
Welsh,J
中科院分区:
生物学3区
文献类型:
--
作者:
Trenkle,T;McClelland,M;Adlkofer,K;Welsh,J

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VAV 3是VAV癌基因家族的新成员,与VAV和VAV 2具有很强的同源性。cDNA的概念性翻译表明,VAV 3在所有鉴定的功能基序中在氨基酸水平上与VAV和VAV 2具有40%至77%的同一性。这种同源性表明VAV 3在信号传导中占据与其他家族成员相似的位置。在人类和小鼠中发现的主要变体转录物VAV 3.1似乎仅编码3′ SH 3-SH 2-SH 3区域,这表明它可能在由该结构域介导的功能中取代全长同种型,或在由更多N-末端基序介导的功能中与全长同种型竞争。VAV 3.1是部分未剪接的mRNA或来源于不同的启动子。VAV 3转录物存在于造血来源的细胞中,其中VAV主要表达。然而,与VAV不同的是,VAV 3和VAV 3.1转录本也以不同的水平存在于各种其他组织和细胞系中。TGF-β和EGF可逆地下调HaCaT角质形成细胞中VAV 3.1转录物的丰度,这代表了生长因子对VAV家族成员的转录物调节的首次观察。
VAV3 is a new member of the VAV oncogene family with a strong homology to VAV and VAV2. A conceptual translation of the cDNA indicates that VAV3 is between 40 and 77% identical to VAV and VAV2 at the amino acid level in all identified functional motifs. This homology suggests that VAV3 occupies a similar position in signal transduction as the other family members. A major variant transcript, VAV3.1, found in both humans and mice, appears to encode only the 3′ SH3–SH2–SH3 region, which suggests that it may substitute for the full-length isoform in functions mediated by this domain, or compete with the full-length isoform in functions mediated by more N-terminal motifs. VAV3.1 either is a partly unspliced mRNA or originates from a different promoter. VAV3 transcripts are found in cells of hematopoietic origin, where VAV is primarily expressed. However, unlike, VAV, the VAV3 and VAV3.1 transcripts are also found at varying levels in a wide variety of other tissues and cell lines. TGF-beta and EGF reversibly down-regulate the abundance of the VAV3.1 transcript in HaCaT keratinocytes, representing the first observation of transcript regulation of a member of the VAV family by a growth factor.