UNLIGANDED C-ERBA THYROID-HORMONE RECEPTOR INDUCES TRKB EXPRESSION INNEUROBLASTOMA-CELLS

Neurotrophins are responsible for the differentiation and survival of neurons in the developing and in the adult nervous system. They bind t o specific membrane receptors with tyrosine kinase activity whose prot otype is the product of the trkA proto-oncogene. TrkB, a member of thi s family, is the receptor for the neurotrophins brain derived growth f actor (BDNF) and neurotrophins-3, 4/5. In this study, we show that sta ble expression of the c-erbA proto-oncogene, which encodes the alpha1- isoform of the nuclear receptor for thyroid hormone (Tralpha1) induces the expression of trkB mRNA with a concomitant decrease to undetectab le levels of trkA and trkC mRNAs in the mouse neuroblastoma N2a cell l ine. trkB induction by c-erbA is ligand independent, since addition of T3 had no effect. The induced trkB transcript encodes a functional gp 145trkB protein, which is phosphorylated on tyrosine in response to BD NF. Furthermore, induction of trkB mRNA is also caused by transient ex pression of either TR alpha1 or beta1 isoforms. Our results are compat ible with the idea that there are certain pathways which are under con trol of unliganded thyroid hormone receptor, and that one of these pat hways results in regulation of trk expression.