The cysteine of the cytoplasmic tail of glucose-dependent insulinotropic peptide receptor mediates its chronic desensitization and down-regulation.
The cysteine of the cytoplasmic tail of glucose-dependent insulinotropic peptide receptor mediates its chronic desensitization and down-regulation.
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葡萄糖依赖性促胰岛素肽受体胞质尾部的半胱氨酸介导其慢性脱敏和下调。
DOI：
10.1016/s0303-7207(98)00061-6
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发表时间：
1998
影响因子：
4.1
通讯作者：
Zhang,XY
中科院分区：
文献类型：
--
作者：
Tseng,CC;Zhang,XY
The glucose-dependent insulinotropic peptide receptor (GIP-R) is a member of G-protein-coupled, seven transmembrane-spanning receptors. Recent studies have shown that elevated serum GIP level in diabetic patients may induce chronic desensitization of the GIP-R, and that this mechanism could contribute to impaired insulin secretion. The cellular basis of down-regulation and chronic desensitization of GIP-R is unclear. To explore the role of the carboxyl terminus of the GIP-R in mediating these processes, five truncated GIP-Rs (T395, T399, T420, T431, T455) were created to delete consecutive serines from the carboxyl end. All mutants except T395exhibit an identical ligand-binding affinity to the WT receptor. The T395mutant, which had the entire carboxyl tail removed, does not bind to ligand. Down-regulation and desensitization was assessed by measuring the receptor number and the ability of agonist-induced cAMP or [Ca2+] generation after pre-exposure to 10−7M GIP for 24 h. The wild-type (WT) and T420, T431, T455mutant GIP-Rs are maximally down-regulated by GIP preincubation, whereas T399mutant does not, indicating that the sequence between amino acids 399 and 420 is critical for this process. Mutation analysis of this area by alanine scanning mutagenesis reveals two critical residues: serine 406 and cysteine 411. Replacement of serine 406 with arginine (S406R) or alanine (S406A) partly attenuates agonist-induced down-regulation and desensitization. In contrast, mutation of the cysteine 411 to glycine (C411G) or alanine (C411A) markedly attenuates both processes. Mutant SCRG, in which both serine 406 and cysteine 411 are mutated, behaves similar to C411G or C411A. The data suggest that chronic desensitization and down-regulation of the GIP-R may be mediated by similar mechanisms, and that the cysteine in the carboxyl terminus plays an essential role in regulating both processes.
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子宫内酒精暴露和儿童出生后四年内的功能缺陷。
DOI：
10.1002/9780470720868.ch11
发表时间：
1984
期刊：
Ciba Foundation symposium
影响因子：
--
作者：
Streissguth,AP;Barr,HM;Martin,DC
通讯作者：
Martin,DC
母亲饮酒和吸烟及其对新生儿调理的影响。
DOI：
10.1111/j.1530-0277.1977.tb05879.x
发表时间：
1977
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
J. Martin;D. C. Martin;C. A. Lund;A. Streissguth
通讯作者：
A. Streissguth
影响因子：
1.4
作者：
H. Spohr;H. Steinhausen
通讯作者：
H. Spohr;H. Steinhausen
母亲饮酒对新生儿状态调节的影响
影响因子：
3.8
作者：
H. Rosett;Patricia Snyder Louis;W. Sander;Austin Lee;Peter Cook;L. Weiner;J. Gould
通讯作者：
J. Gould
DOI：
10.1111/j.1651-2227.1985.tb10915.x
发表时间：
1985-01-01
期刊：
ACTA PAEDIATRICA SCANDINAVICA
影响因子：
--
作者：
KYLLERMAN, M;ARONSON, M;OLEGARD, R
通讯作者：
OLEGARD, R