ERYTHROPOIETIN RECEPTORS INDUCED BY DIMETHYL-SULFOXIDE EXHIBIT POSITIVE COOPERATIVITY ASSOCIATED WITH AN AMPLIFIED BIOLOGIC RESPONSE

被引:14
作者
YONEKURA, S [1 ]
CHERN, YJ [1 ]
DONAHUE, KA [1 ]
FELDMAN, L [1 ]
VANASSE, GJ [1 ]
SYTKOWSKI, AJ [1 ]
机构
[1] HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,DIV HEMATOL & ONCOL,BOSTON,MA 02215
关键词
ERYTHROCYTES; SIGNAL TRANSDUCTION; ERYTHROPOIESIS; DIFFERENTIATION; RAUSCHER MURINE ERYTHROLEUKEMIA CELLS;
D O I
10.1073/pnas.88.6.2535
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Erythropoietin triggers the differentiation of erythrocyte progenitors by binding to receptors on their plasma membrane. We report here that pretreatment of erythropoietin-responsive murine erythroleukemia cells with chemical inducers resulted in a striking increase in erythropoietin-specific hemoglobinization. This amplification of the erythropoietin biologic response was accompanied by the induction of a new population of high-density receptors (almost-equal-to 20,000 per cell) exhibiting marked positive cooperativity. Erythropoietin binding to new receptors displayed a convex upward Scatchard plot and a Hill coefficient (nH) of 6.75. Measurement of erythropoietin receptor mRNA demonstrated an initial decrease in receptor transcript followed by an approximately 2- to 3-fold increase after 24-48 hr. This increase in receptor message does not appear to account for the magnitude of the receptor up-regulation by dimethyl sulfoxide. We propose that this positive cooperativity reflects the interaction (clustering) of receptors, presumably through the formation of homooligomers or heterooligomers, and that this receptor interaction may amplify the erythropoietin signal transduction pathway.
引用
收藏
页码:2535 / 2539
页数:5
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