Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene.
Nerve growth factor (NGF) is required for the development and survival of sympathetic and neural crest-derived sensory neurons. The mechanism of action of NGF has been extensively studied in the NGF-responsive rat pheochromocytoma cell line, PC12. When treated with NGF, PC12 cells initiate neurite outgrowth and differentiate into cells with a neuronal phenotype. This process is prevented by RNA synthesis inhibitors. NGFI-B is a gene, identified by differential hybridization, that is rapidly, but transiently induced in PC12 cells by NGF. The nucleotide sequence of the NGFI-B gene was determined, and it encodes a 61 kd protein with strong homologies to members of the glucocorticoid receptor gene family. The two regions of homology between NGFI-B and this family of ligand-dependent transcriptional activators are the region corresponding to the DNA-binding domain and the region comprising the ligand-binding domain near the COOH-terminus. NGFI-B, as a possible ligand-dependent transcriptional activator induced by NGF, may play a role in initiating NGF-induced differentiation.
Milbrandt
J
J
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010673:Pheochromocytoma; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects
D004268:DNA-Binding Proteins; D009414:Nerve Growth Factors; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D014157:Transcription Factors