DIFFERENTIAL EXPRESSION OF NERVE GROWTH-FACTOR RECEPTORS LEADS TO ALTERED BINDING-AFFINITY AND NEUROTROPHIN RESPONSIVENESS

被引:267
作者
BENEDETTI, M [1 ]
LEVI, A [1 ]
CHAO, MV [1 ]
机构
[1] CORNELL UNIV,MED CTR,COLL MED,DEPT CELL BIOL & ANAT,DIV HEMATOL ONCOL,NEW YORK,NY 10021
关键词
TRK RECEPTOR; NEUROTROPHIN-3; HIGH-AFFINITY BINDING;
D O I
10.1073/pnas.90.16.7859
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
The low-affinity p75 neurotrophin receptor is believed to participate with the Trk receptor tyrosine kinase in the formation of high-affinity binding sites for nerve growth factor (NGF). To investigate the functional significance of the two NGF receptors, a truncated p75 receptor was stably expressed in PC12 rat pheochromocytoma cells, yielding cells with greatly reduced levels of wild-type p75 and normal Trk levels. Although these cells were capable of normal differentiation by NGF, very few high-affinity NGF binding sites were detected. These findings indicate that high-affinity binding may be functionally dissociated from biological responses. Furthermore, an increased responsiveness to neurotrophin 3 was observed, as manifested by increased neurite outgrowth. These results suggest that a correct ratio of p75 and p140trk is required to create high-affinity sites and that p75 expression may assist in the discrimination between related but different neurotrophin factors.
引用
收藏
页码:7859 / 7863
页数:5
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