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Science 26 April 1991:
Vol. 252. no. 5005, pp. 561 - 563
DOI: 10.1126/science.1850551

Articles

Science, Vol 252, Issue 5005, 561-563
Copyright © 1991 by American Association for the Advancement of Science


articles

Chimeric NGF-EGF receptors define domains responsible for neuronal differentiation

H Yan, J Schlessinger, and MV Chao

Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY 10021.

To determine the domains of the low-affinity nerve growth factor (NGF) receptor required for appropriate signal transduction, a series of hybrid receptors were constructed that consisted of the extracellular ligand-binding domain of the human epidermal growth factor (EGF) receptor (EGFR) fused to the transmembrane and cytoplasmic domains of the human low-affinity NGF receptor (NGFR). Transfection of these chimeric receptors into rat pheochromocytoma PC12 cells resulted in appropriate cell surface expression. Biological activity mediated by the EGF-NGF chimeric receptor was assayed by the induction of neurite outgrowth in response to EGF in stably transfected cells. Furthermore, the chimeric receptor mediated nuclear signaling, as evidenced by the specific induction of transin messenger RNA, an NGF-responsive gene. Neurite outgrowth was not observed with chimeric receptors that contained the transmembrane domain from the EGFR, suggesting that the membrane-spanning region and cytoplasmic domain of the low-affinity NGFR are necessary for signal transduction.


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