Unliganded c-erbA/thyroid hormone receptor induces trkB expression in neuroblastoma cells.
Neurotrophins are responsible for the differentiation and survival of neurons in the developing and in the adult nervous system. They bind to specific membrane receptors with tyrosine kinase activity whose prototype is the product of the trkA proto-oncogene. TrkB, a member of this family, is the receptor for the neurotrophins brain derived growth factor (BDNF) and neurotrophins-3, -4/5. In this study, we show that stable expression of the c-erbA proto-oncogene, which encodes the alpha 1-isoform of the nuclear receptor for thyroid hormone (Tr alpha 1) induces the expression of trkB mRNA with a concomitant decrease to undetectable levels of trkA and trkC mRNAs in the mouse neuroblastoma N2a cell line. trkB induction by c-erbA is ligand independent, since addition of T3 had no effect. The induced trkB transcript encodes a functional gp145trkB protein, which is phosphorylated on tyrosine in response to BDNF. Furthermore, induction of trkB mRNA is also caused by transient expression of either TR alpha 1 or beta 1 isoforms. Our results are compatible with the idea that there are certain pathways which are under control of unliganded thyroid hormone receptor, and that one of these pathways results in regulation of trk expression.
Pastor
R
R
Instituto Investigaciones Biomédicas, (CSIC), Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Bernal
J
J
Rodríguez-Peña
A
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002454:Cell Differentiation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009447:Neuroblastoma / Q000235:genetics*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; D017978:Receptors, Growth Factor / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D013963:Thyroid Hormones / Q000494:pharmacology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; C019277:brain-derived growth factor; D005576:Colforsin; D014212:Tretinoin; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC