Chimeric NGF-EGF receptors define domains responsible for neuronal differentiation.
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.
Yan
H
H
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY 10021.
Schlessinger
J
J
Chao
M V
MV
D000310:Adrenal Gland Neoplasms; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002454:Cell Differentiation; D002460:Cell Line; D002678:Chimera; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D010673:Pheochromocytoma; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor; D014162:Transfection
D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors