MOLECULAR PHYSIOLOGY OF BAND 3-LIKE PROTEINS OF KIDNEY

肾脏带 3 样蛋白的分子生理学

基本信息

批准号：
2391438
负责人：
SETH Leo ALPER
金额：
$ 22.67万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-01-15 至 1998-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2391438
关键词：
Xenopus oocyte acidity /alkalinity band 3 protein chemical binding fatty acylation glycosylation kidney cell molecular cloning protein isoforms protein structure function site directed mutagenesis tissue /cell culture transfection

项目摘要

SPECIFIC AIMS Our overall objective is to characterize the functional and regulatory properties (common and distinct) of the AE anion exchanger gene family proteins, and to ascribe those properties to defined amino acid residues or domains of the proteins. The proposed experiments are designed to develop an understanding of the mechanisms by which the AE anion exchanger proteins function as regulated ion transporters and interact directly with other proteins. To accomplish these objectives, we propose: 1. To extend the functional analyses of AE1, AE2, and AE3 isoforms in two heterologous expression systems: the Xenopus oocyte and the transiently transfected CHOP cell. 2. To assess the functional and biochemical properties of proteins encoded by defined mutant AE1 cDNAs from patients with hereditary spherocytosis and other erythroid disorders. To mutate AE2 and AE3 in those conserved residues and assess the functional consequences. 3. To define the molecular bases of AE protein regulation by defining the amino acids which mediate various regulatory influences: 4. To ascertain the role of oligomerization state, glycosylation, and fatty acylation on the function and regulation of AE1, AE2, and AE3. 5. To create and select for second-site revertants in loss-of-function mutants, in order to provide information on secondary and tertiary structure of AE proteins. 6. To identify, clone, and characterize proteins which bind to the cytoplasmic domains of AE2 and AE3, and to delineate their binding sites within the AE protein sequences.

具体目标我们的总体目标是描述功能和监管的特征 AE 阴离子交换基因家族的特性（共同点和独特点）蛋白质，并将这些特性归因于定义的氨基酸残基或蛋白质的结构域。所提出的实验旨在了解 AE 阴离子的作用机制交换蛋白充当调节离子转运蛋白并相互作用直接与其他蛋白质结合。为了实现这些目标，我们建议： 1. 将 AE1、AE2 和 AE3 亚型的功能分析扩展到两种异源表达系统：非洲爪蟾卵母细胞和瞬时表达系统转染CHOP细胞。 2. 评估蛋白质的功能和生化特性由遗传性患者的特定突变 AE1 cDNA 编码球形红细胞增多症和其他红细胞疾病。突变 AE2 和 AE3 那些保守的残基并评估功能后果。 3. 通过定义AE蛋白调节的分子基础介导各种调节影响的氨基酸： 4. 确定寡聚状态、糖基化和脂肪酰化对 AE1、AE2 和 AE3 功能和调节的影响。 5. 创建和选择功能丧失的第二位点回复体突变体，以提供有关二级和三级的信息 AE蛋白的结构。 6. 鉴定、克隆和表征与 AE2 和 AE3 的胞质结构域，并描绘它们的结合位点 AE 蛋白序列内。

项目成果

期刊论文数量（60）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Modulation of c-fos and egr-1 expression in the isolated perfused kidney by agents that alter tubular work.

通过改变肾小管工作的药物调节离体灌注肾中的 c-fos 和 egr-1 表达。

DOI：
10.1038/ki.1997.312
发表时间：
1997
期刊：
Kidney international
影响因子：
19.6
作者：
Joannidis,M;Cantley,LG;Spokes,K;Stuart-Tilley,AK;Alper,SL;Epstein,FH
通讯作者：
Epstein,FH

Chromosomal location of the murine anion exchanger genes encoding AE2 and AE3.

编码 AE2 和 AE3 的鼠阴离子交换基因的染色体位置。

DOI：
10.1007/bf00292027
发表时间：
1994
期刊：
Mammalian genome : official journal of the International Mammalian Genome Society
影响因子：
0
作者：
White,RA;Geissler,EN;Adkison,LR;Dowler,LL;Alper,SL;Lux,SE
通讯作者：
Lux,SE

Autosomal dominant polycystic kidney disease decreases anion exchanger activity.

常染色体显性多囊肾病会降低阴离子交换活性。

DOI：
10.1152/ajpcell.1997.272.5.c1748
发表时间：
1997
期刊：
The American journal of physiology.
影响因子：
0
作者：
Perrone,RD;Grubman,SA;Murray,SL;Lee,DW;Alper,SL;Jefferson,DM
通讯作者：
Jefferson,DM

Increased sulfate uptake by E. coli overexpressing the SLC26-related SulP protein Rv1739c from Mycobacterium tuberculosis.

过度表达来自结核分枝杆菌的 SLC26 相关 SulP 蛋白 Rv1739c 的大肠杆菌增加了硫酸盐的摄取。

DOI：
10.1016/j.cbpa.2007.12.005
发表时间：
2008
期刊：
Comparative biochemistry and physiology. Part A, Molecular & integrative physiology
影响因子：
0
作者：
Zolotarev,AlexanderS;Unnikrishnan,Meera;Shmukler,BorisE;Clark,JeffreyS;Vandorpe,DavidH;Grigorieff,Nikolaus;Rubin,EricJ;Alper,SethL
通讯作者：
Alper,SethL

Electrogenic sulfate/chloride exchange in Xenopus oocytes mediated by murine AE1 E699Q.