Activation of erythropoietin receptor through a novel extracellular binding site

被引：17

作者：

Naranda, T

Kaufman, RI

Li, J

Wong, K

Boge, A

Hallén, D

Fung, KYC

Duncan, MW

Andersen, N

Goldstein, A

Olsson, L ^{[1
]}

机构：

[1] Receptron Inc, Mt View, CA 94043 USA

[2] Pharmacia Corp, SE-11276 Stockholm, Sweden

[3] Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA

[4] Univ Washington, Dept Chem, Seattle, WA 98195 USA

[5] Stanford Univ, Stanford, CA 95305 USA

来源：

ENDOCRINOLOGY | 2002年 / 143卷 / 06期

关键词：

D O I：

10.1210/en.143.6.2293

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Activation of erythropoietin (EPO) receptor (EPOR) by a small peptide (ERP) was reported previously. ERP binds to a different receptor site than EPO, and binding of ERP does not change the dissociation constant and maximal binding for EPO binding to the receptor. The extracellular binding site for ERP is now characterized. The site is located in the membrane proximal, extracellular part of the receptor. ERP binds to a region on the EPOR that contains the same sequence as ERP. It is speculated that ERP binds to its identical sequence on EPOR, as ERP self-interacts. ERP is specific for EPOR and associates noncovalently with EPOR in a ratio 1:1. Peptide binding to the receptor results in receptor-mediated cellular proliferation, intracellular signaling, and erythroid colony-forming unit formation in bone marrow cells. The activity is comparable to that of EPO. Recognition of such receptor sites represents a new and important concept in receptor function.

引用

页码：2293 / 2302

页数：10

共 23 条

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