PMID- 12111796
OWN - NLM
STAT- MEDLINE
DCOM- 20020814
LR  - 20161124
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 69
IP  - 2
DP  - 2002 Jul 15
TI  - BDNF activated TrkB/IRR receptor chimera promotes survival of sympathetic neurons 
      through Ras and PI-3 kinase signaling.
PG  - 151-9
AB  - 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.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Kelly-Spratt, Karen S
AU  - Kelly-Spratt KS
AD  - Center For Developmental Biology, University of Texas Southwestern Medical 
      Center, Dallas, Texas 75235-9133, USA.
FAU - Klesse, Laura J
AU  - Klesse LJ
FAU - Parada, Luis F
AU  - Parada LF
LA  - eng
GR  - 5R37-NS33199/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (insulin receptor-related receptor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Culture Techniques
MH  - Cell Survival
MH  - *Genes, ras
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - PC12 Cells
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Rats
MH  - Receptor, Insulin/*metabolism
MH  - Receptor, trkB/*metabolism
MH  - Recombinant Fusion Proteins/*metabolism
MH  - Second Messenger Systems
MH  - Superior Cervical Ganglion/enzymology/*metabolism
MH  - Time Factors
EDAT- 2002/07/12 10:00
MHDA- 2002/08/15 10:01
CRDT- 2002/07/12 10:00
PHST- 2002/07/12 10:00 [pubmed]
PHST- 2002/08/15 10:01 [medline]
PHST- 2002/07/12 10:00 [entrez]
AID - 10.1002/jnr.10172 [doi]
PST - ppublish
SO  - J Neurosci Res. 2002 Jul 15;69(2):151-9. doi: 10.1002/jnr.10172.