CHIMERIC TUMOR NECROSIS FACTOR-TRKA RECEPTORS REVEAL THAT LIGAND-DEPENDENT ACTIVATION OF THE TRKA TYROSINE KINASE IS SUFFICIENT FOR DIFFERENTIATION AND SURVIVAL OF PC12 CELLS

被引：51

作者：

ROVELLI, G ^{[1
]}

HELLER, RA ^{[1
]}

CANOSSA, M ^{[1
]}

SHOOTER, EM ^{[1
]}

机构：

[1] SYNTEX DISCOVERY RES,INST BIOCHEM & CELL BIOL,PALO ALTO,CA 94304

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1993年 / 90卷 / 18期

关键词：

D O I：

10.1073/pnas.90.18.8717

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：

To elucidate the function of the two nerve growth factor (NGF) receptors, p75NGFR and p140trk, chimeric molecules were constructed of tumor necrosis factor (TNF) and NGF receptors. Rat PC12 pheochromocytoma cells transiently transfected with TNF-p140trk chimeras, which contain the extracellular domain of TNF receptor and the transmembrane and cytoplasmic domains of p140trk, showed TNF-dependent neuronal differentiation and cell survival. The activity of TNF-p140trk chimeras was completely blocked by the tyrosine kinase inhibitor K252a, and TNF was unable to induce neurite elongation in PC12 cells transfected with a tyrosine kinase-defective chimeric receptor. The TNF-p75NGFR chimeras, which contain the cytoplasmic domain of p75NGFR, were nonfunctional. Our results suggest that p140trk may function as ligand-activated homodimers and that ligand-mediated activation of the cytoplasmic domain of p140trk alone is sufficient for inducing a neuronal phenotype.

引用

页码：8717 / 8721

页数：5

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