BDNF activated TrkB/IRR receptor chimera promotes survival of sympathetic neurons through ras and PI-3 kinase signaling

Karen S. Kelly-Spratt, Laura J. Klesse, Luis F. Parada

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Insulin receptor-related receptor (IRR) expression is tightly coupled to the nerve growth factor (NGF) receptor, TrkA, throughout development. Expression of both receptors is primarily localized to neural crest derived sensory and sympathetic neurons. In contrast to TrkA, however, the physiological ligand for IRR is unknown. To analyze the intracellular signaling and potential function of the orphan IRR in neurons, an adenovirus expressing a TrkB/IRR chimeric receptor was used to infect cultured mouse superior cervical ganglion neurons that normally require NGF for survival. Brain derived neurotrophic factor (BDNF)-activated TrkB/IRR induced neuronal survival. We utilized numerous receptor mutants in order to identify the intracellular domains of IRR necessary for signaling and neuron survival. Finally, we employed adenovirus encoding dominant negative forms of the extracellular signal-regulated kinase (ERK) signaling cascade to demonstrate that IRR, like TrkA, requires ras activation to promote neuron survival. Therefore, by use of the chimeric TrkB/IRR receptor, we have demonstrated the ability of IRR to elicit activation of signaling cascades resulting in a biological response in superior cervical ganglion (SCG) neurons.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalJournal of Neuroscience Research
Volume69
Issue number2
DOIs
StatePublished - Jul 15 2002

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trkB Receptor
Brain-Derived Neurotrophic Factor
Phosphatidylinositol 3-Kinases
Neurons
Superior Cervical Ganglion
Adenoviridae
insulin receptor-related receptor
Nerve Growth Factor Receptor
Neural Crest
Extracellular Signal-Regulated MAP Kinases
Nerve Growth Factor
Sensory Receptor Cells
Ligands

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

BDNF activated TrkB/IRR receptor chimera promotes survival of sympathetic neurons through ras and PI-3 kinase signaling. / Kelly-Spratt, Karen S.; Klesse, Laura J.; Parada, Luis F.

In: Journal of Neuroscience Research, Vol. 69, No. 2, 15.07.2002, p. 151-159.

Research output: Contribution to journalArticle

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