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.