PMID- 10567924
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20220129
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 182
IP  - 1
DP  - 2000 Jan
TI  - The Gly571Arg mutation, associated with the autonomic and sensory disorder 
      congenital insensitivity to pain with anhidrosis, causes the inactivation of the 
      NTRK1/nerve growth factor receptor.
PG  - 127-33
AB  - Point mutations affecting the NTRK1/TRKA gene, encoding one of the receptors for 
      the nerve growth factor (NGF), have been detected in congenital insensitivity to 
      pain with anhidrosis (CIPA), a human hereditary sensory neuropathy characterized 
      by absence of reaction to noxious stimuli and anhidrosis. To define the defect of 
      NTRK1 in CIPA patients, we have introduced one of the previously reported 
      mutations (Gly571Arg) into both the NTRK1 and the TRK-T3 oncogene cDNAs. The 
      expression of the mutated constructs into COS1 cells revealed that the introduced 
      mutation, while not affecting its correct membrane localization, rendered the 
      NTRK1 protein unable to undergo activation upon stimulation with NGF. Similarly, 
      the mutation abolished the constitutive activation of the TRK-T3 oncogene. 
      Transfection into NIH3T3 and PC12 cells showed the loss of transforming and 
      differentiating activity by the mutated constructs. Our results demonstrate 
      clearly that the CIPA mutations cause the inactivation of the NTRK1 receptor, 
      thus exerting a loss of function effect, and provide an experimental approach to 
      distinguish functional mutations from genetic polymorphisms.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Greco, A
AU  - Greco A
AD  - Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy. 
      greco@istitutotumori.mi.it
FAU - Villa, R
AU  - Villa R
FAU - Fusetti, L
AU  - Fusetti L
FAU - Orlandi, R
AU  - Orlandi R
FAU - Pierotti, M A
AU  - Pierotti MA
LA  - eng
GR  - E.0568/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Amino Acid Substitution/*genetics
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cell Transformation, Neoplastic/drug effects
MH  - Gene Expression
MH  - Hereditary Sensory and Autonomic Neuropathies/*genetics
MH  - Humans
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Mutation/*genetics
MH  - Nerve Growth Factor/pharmacology
MH  - Neurites/drug effects
MH  - Phenotype
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Rats
MH  - Receptor, trkA/*genetics/*metabolism
MH  - Transfection
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1002/(SICI)1097-4652(200001)182:1<127::AID-JCP14>3.0.CO;2-0 [pii]
AID - 10.1002/(SICI)1097-4652(200001)182:1<127::AID-JCP14>3.0.CO;2-0 [doi]
PST - ppublish
SO  - J Cell Physiol. 2000 Jan;182(1):127-33. doi: 
      10.1002/(SICI)1097-4652(200001)182:1<127::AID-JCP14>3.0.CO;2-0.