Repeated administration of phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor blocker, produces schizophrenia-like behaviors in humans and rodents. Although impairment of synaptic function has been implicated in the effect of PCP, the molecular mechanisms have not yet been elucidated. Considering that brain-derived neurotrophic factor (BDNF) plays an important role in sy...

The development of the peripheral nervous system is governed in part by a family of neurotrophic factors that signal through Trk tyrosine kinase receptors. Neurotrophin 3 (NT3) ablation in mice causes a more severe neuronal phenotype than deletion of its receptor TrkC, suggesting that NT3 acts also through other non-preferred Trk receptors. To study the role of low-affinity ligand receptor inte...

Differentiation and function of pancreatic beta cells are regulated by a variety of hormones and growth factors, including nerve growth factor (NGF). Whether this is an endocrine or autocrine/paracrine role for NGF is not known. We demonstrate that NGF is produced and secreted by adult rat pancreatic beta cells. NGF secretion is increased in response to elevated glucose or potassium, but decrea...

A large number of poor prognosis neuroblastoma (NB) tumors constitutively express brain-derived neurotrophic factor (BDNF) and variably express the gene for its tyrosine kinase (Trk) receptor TrkB. Good prognosis NB tumors typically express high levels of TrkA mRNA, which encodes the signal transducing receptor for nerve growth factor, p140TrkA. These neurotrophins are necessary for neural cell...

Neurotrophins are key regulators of neuronal survival and differentiation during development. Activation of their cognate receptors, Trk receptors, a family of receptor tyrosine kinases (RTKs), is pivotal for mediating the downstream functions of neurotrophins. Recent studies reveal that cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase, may modulate RTK signaling through phosphorylat...

Stimulation of potassium uptake is the most rapid response to an osmotic upshock in bacteria. This cation accumulates by a number of different transport systems whose importance has not been previously addressed for rhizobia. In silico analyses reveal the presence of genes encoding four possible potassium uptake systems in the genome of Sinorhizobium meliloti 1021: Kup1, Kup2, Trk, and Kdp. The...

The nerve growth factor (NGF) family of neurotrophins binds two classes of cell-surface receptors, trk receptor tyrosine kinases and the shared p75 receptor. Rapid internalization and retrograde trafficking of neurotrophin-trk complexes have been demonstrated in a number of systems and are thought to transmit trophic signals from terminals to neuronal cell bodies. In contrast, the internalizati...

We have identified and cloned a new member of the trk gene family, termed trkE, which generates a 3.9-kilobase (kb) transcript in normal human keratinocytes and in a variety of normal human tissues, but not in liver. Albeit at low level, trkE transcript is expressed also by PC12 cells. The open reading frame codes for a polypeptide of 876 amino acids exhibiting the classic features of cell surf...

The gene for the Thermotoga maritima Trk potassium transporter component TrkA was originally thought to be a frameshift mutation and not to encode a functional protein. However, expression from this gene yielded a complex consisting of two distinct proteins designated TM1088A and -B. Genetic complementation of Escherichia coli mutants unable to transport potassium suggests that TM1088A/B is par...

The neurotrophin family of proteins are believed to mediate various forms of synaptic plasticity in the adult brain. Here we have assessed the roles of these proteins in object recognition memory in the rat, using icv infusions of function-blocking antibodies or the tyrosine kinase antagonist, tyrphostin AG879, to block Trk receptors. We report that tyrphostin AG879 impairs both short-term and ...