CLONING AND CHARACTERIZATION OF HDLG - THE HUMAN HOMOLOG OF THE DROSOPHILA DISKS LARGE TUMOR-SUPPRESSOR BINDS TO PROTEIN-4.1

CLONING AND CHARACTERIZATION OF HDLG - THE HUMAN HOMOLOG OF THE DROSOPHILA DISKS LARGE TUMOR-SUPPRESSOR BINDS TO PROTEIN-4.1
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DOI:
10.1073/pnas.91.21.9818
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发表时间:
1994-10-11
影响因子:
11.1
通讯作者:
CHISHTI, AH
CHISHTI, AH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LUE, RA;MARFATIA, SM;CHISHTI, AH

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果蝇圆盘大肿瘤抑制蛋白 dlg 已被证明在胚胎发生过程中调节成虫盘的生长 [Woods, D. F. & Bryant, P. J. (1991) Cell 66, 451-464]。我们克隆并测序了人类 B 淋巴细胞 100-kDa 蛋白的完整 cDNA,该蛋白与 dlg 具有 60% 的氨基酸同一性。这种果蝇大圆盘 (hdlg) 的人类同源物包含与已知鸟苷酸激酶同源的 C 末端结构域、一个 src 同源 3 区域蛾和三个 dlg 同源重复序列。可以包含框内插入的两个非同源结构域导致至少四种选择性剪接的 hdlg 同工型。几种 hdlg RNA 转录物广泛分布于人和鼠组织中,并且该蛋白质定位于细胞与细胞接触的区域。蛋白 4.1 是包含 talin 和 merlin/schwannomin 在内的家族的定义成员,具有与 hdlg 相同的细胞定位,并且 hdlg 内的两个位点在体外与蛋白 4.1 的 30 kDa N 端结构域相关。
The Drosophila discs large tumor suppressor protein, dlg, has been shown to regulate the growth of imaginal discs during embryogenesis [Woods, D. F. & Bryant, P. J. (1991) Cell 66, 451-464]. We cloned and sequenced the complete cDNA for a human B-lymphocyte 100-kDa protein that shares 60% amino acid identity with dlg. This human homologue of Drosophila discs large (hdlg) contains a C-terminal domain homologous to the known guanylate kinases, a src homology 3 region moth, and three dlg homology repeats. Two nonhomologous domains that can contain in-frame insertions result in at least four alternatively spliced isoforms of hdlg. Several hdlg RNA transcripts are widely distributed in human and murine tissues, and the protein is localized to regions of cell-cell contact. Protein 4.1, the defining member of a family that includes talin and merlin/schwannomin, has the same cellular localization as hdlg, and two sites within hdlg associate in vitro with the 30-kDa N-terminal domain of protein 4.1.