To facilitate an understanding of injury-induced changes within the nervous system, we used a single-cell, in vitro model of axonal injury. Sensory neurons were individually dissociated from the CNS of Aplysia and placed into cell culture. The major neurite of some neurons was then transected (axotomized neurons). Axotomy in hemolymph-containing culture medium produced long-term hyperexcitabili...

The neurotrophins (NTs) play a key role in neuronal survival and maintenance. The TRK (tropomyosin-related kinase) tyrosine kinase receptors (TRKA, TRKB, TRKC) are high affinity receptors for NTs. There is increasing data demonstrating an important role of the TRK family in cancer initiation and progression. NTs have been known for many years to promote chemotaxis, maturation, and survival of m...

UNLABELLED Pectobacterium wasabiae (previously known as Erwinia carotovora) is an important plant pathogen that regulates the production of plant cell wall-degrading enzymes through an N-acyl homoserine lactone-based quorum sensing system and through the GacS/GacA two-component system (also known as ExpS/ExpA). At high cell density, activation of GacS/GacA induces the expression of RsmB, a nonc...

Neurotrophins can mediate survival or death of neurons. Opposing functions of neurotrophins are based on binding of these ligands to two distinct types of receptors: trk receptors and p75NTR. Previous work showed that target-derived NGF induces cell death, whereas BDNF and NT-3 enhance survival of neurons in the isthmo-optic nucleus of avian embryos. To determine the fate of retrogradely transp...

Abstract On-target resistance to next-generation TRK inhibitors in fusion–positive cancers is largely uncharacterized. In patients with these tumors, we found that xDFG mutations confer type I designed maintain potency against several kinase domain mutations. Computational modeling and biochemical assays showed TRKAG667 TRKCG696 substitutions reduce drug binding by generating steric hindrance. ...

Neurotrophism, structural plasticity, learning and long-term memory in mammals critically depend on neurotrophins binding Trk receptors to activate tyrosine kinase (TyrK) signaling, but Drosophila lacks full-length Trks, raising the question of how these processes occur in the fly. Paradoxically, truncated Trk isoforms lacking the TyrK predominate in the adult human brain, but whether they have...

The indolocarbazole analogue CEP-751 is a potent and selective tyrosine kinase inhibitor of the neurotrophin-specific trk receptors that has demonstrated antitumor activity in nine different models of prostate cancer growth in vivo. In the slow-growing, androgen-sensitive Dunning H prostate cancers, which express trk receptors, CEP-751 induced transient regressions independent of effects on cel...

We have shown previously that BDNF, neurotrophin-3 (NT-3), chlorphenylthio-cAMP (cpt-cAMP) (a permeant cAMP analog), and membrane depolarization promote spiral ganglion neuron (SGN) survival in vitro in an additive manner, depolarization having the greatest efficacy. Expression of both BDNF and of NT-3 is detectable in cultured SGNs after plating in either depolarizing or nondepolarizing medium...