Proneurotrophins bind with high affinity to p75 neurotrophin receptor (p75NTR) and lack the capacity to bind Trk receptors, suggesting that proneurotrophins can elicit apoptosis via p75NTR even in cells expressing survival-promoting Trk receptors. In the CNS, basal forebrain (BF) neurons are particularly vulnerable to degeneration in Alzheimer's disease, and are among the few populations of bra...

The human tumorous imaginal disc 1 (TID1) proteins including TID1(L) and TID1(S), members of the DnaJ domain protein family, are involved in multiple intracellular signaling pathways such as apoptosis induction, cell proliferation, and survival. Here we report that TID1 associates with the Trk receptor tyrosine kinases and regulates nerve growth factor (NGF)-induced neurite outgrowth in PC12-de...

Receptor-type protein tyrosine phosphatases (RPTPs) have been implicated as direct or indirect regulators of neurotrophin receptors (TRKs). It remains less clear if and how such RPTPs might regulate TRK proteins in vivo during development. Here we present a comparative expression profile of RPTP genes and Trk genes during early stages of murine, dorsal root ganglion maturation. We find little i...

This study examines how the family of neurotrophin receptor tyrosine kinases (Trks) participates in the regeneration and replacement of olfactory neurons within the adult rat olfactory neuroepithelium. mRNA and protein products representing the high-affinity nerve growth factor (NGF) receptor Trk A, its family members Trk B and Trk C, and the low-affinity NGF receptor (INGFR) are all detected w...

The four mammalian neurotrophins - NGF, BDNF, NT-3 and NT-4 - each bind and activate one or more of the Trk family of receptor tyrosine kinases. Through these receptors, neurotrophins activate many intracellular signaling pathways, including those controlled by Ras, the Cdc42/Rac/RhoG protein family, MAPK, PI3K and PLC-gamma, thereby affecting both development and function of the nervous system...

Specificity of neurotrophin factor signaling is dictated through the action of Trk receptor tyrosine kinases. Once activated, Trk receptors are internalized and targeted for degradation. However, the mechanisms implicated in this process are incompletely understood. Here we report that the Trk receptors are multimonoubiquitinated in response to neurotrophins. We have identified an E3 ubiquitin ...

Oncogenic rearrangements of the NTRK1 gene (also designated TRKA), encoding one of the receptors for the nerve growth factor, are frequently detected in thyroid carcinomas. Such rearrangements fuse the NTRK1 tyrosine kinase domain to 5'-end sequences belonging to different genes. In previously reported studies we have demonstrated that NTRK1 oncogenic activation involves two genes, TPM3 and TPR...

Target-derived neurotrophins initiate signals that begin at nerve terminals and cross long distances to reach the cell bodies and regulate gene expression. Neurotrophin receptors, Trks, themselves serve as retrograde signal carriers. However, it is not yet known whether the retrograde propagation of Trk activation reflects movement of Trk receptors from neurites to cell bodies or reflects seria...

PURPOSE To investigate changes in percentage of tyrosine kinase (trk)A-, trkB-, and trkC-immunopositive ((+)) retinal ganglion cells (RGCs) at various times after optic nerve (ON) axotomy; the proportion of RGCs regenerating axons into peripheral nerve (PN) grafts that are trkA(+), trkB(+), and trkC(+); whether intravitreal PN-ON implants affect trk immunoreactivity; and the levels of trk mRNAs...