CLONING AND CHROMOSOMAL LOCALIZATION OF THE HUMAN TRK-B TYROSINE KINASE RECEPTOR GENE (NTRK2)

CLONING AND CHROMOSOMAL LOCALIZATION OF THE HUMAN TRK-B TYROSINE KINASE RECEPTOR GENE (NTRK2)
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DOI:
10.1016/0888-7543(95)80055-q
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发表时间:
1995-01-20
期刊:
影响因子:
4.4
通讯作者:
BRODEUR, GM
BRODEUR, GM
中科院分区:
生物学3区
文献类型:
--
作者:
NAKAGAWARA, A;LIU, XC;BRODEUR, GM

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越来越多的证据表明神经营养素及其受体在调节中枢和周围神经系统的发育中发挥着重要作用。人类 TRK-A (NTRK1) 和 TRK-C (NTRK3) 已被克隆和测序,但仅公布了人类 TRK-B 的截短形式。因此,我们从人脑 cDNA 文库中分离出跨越人类全长和截短形式 TRK-B 整个编码区的互补 DNA。人类全长 TRK-B 编码 822 个氨基酸残基的蛋白质。推定的成熟肽序列与人TRK-A有49%同源性,与全长人TRK-C有55%同源性,TRK-A、-B和-C之间有40%氨基酸同一性。人TRK-A、-B和-C中13个半胱氨酸残基中的9个、胞外域中12个N-糖基化位点中的4个以及胞内域中13个酪氨酸残基中的10个是保守的。 TRK-B 的近膜区域有一个由 10 个丝氨酸残基组成的簇,而 TRK-A 中则不存在。人脑中表达了两种主要大小的 TRK-B 转录本。使用胞外或酪氨酸激酶结构域特异性探针进行的 Northern 印迹分析显示,9.5 kb 条带编码全长 TRK-B mRNA,8.0 kb 条带编码 TRK-B mRNA 的截短形式。通过荧光原位杂交和体细胞杂交作图,人 TRK-B 基因定位于染色体 9q22.1。 (C) 1995 学术出版社
There is increasing evidence that neurotrophins and their receptors play an important role in regulating development of both the central and the peripheral nervous systems. Human TRK-A (NTRK1) and TRK-C (NTRK3) have been cloned and sequenced, but only a truncated form of human TRK-B has been published. Therefore, we isolated complementary DNAs spanning the entire coding region of both human full-length and truncated forms of TRK-B from human brain cDNA libraries. Human full-length TRK-B codes for a protein of 822 amino acid residues. The putative mature peptide sequence is 49% homologous to human TRK-A and 55% to full-length human TRK-C, with 40% amino acid identity among TRK-A, -B, and -C. Nine of 13 cysteine residues, 4 of 12 N-glycosylation sites in the extracellular domain, and 10 of 13 tyrosine residues in the intracellular domain are conserved among human TRK-A, -B, and -C. There is a cluster of 10 serine residues in the juxtamembrane region of TRK-B that is absent in TRK-A Two major sizes of TRK-B transcripts were expressed in human brain. Northern blot analysis using probes specific for the extracellular or the tyrosine kinase domain revealed that the 9.5-kb band encodes the full-length TRK-B mRNA and the 8.0-kb band encodes the truncated form of TRK-B mRNA By fluorescence in situ hybridization and somatic cell hybrid mapping, the human TRK-B gene was localized to chromosome 9q22.1. (C) 1995 Academic Press, Inc.