PMID- 1326636
OWN - NLM
STAT- MEDLINE
DCOM- 19921019
LR  - 20211203
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 32
IP  - 4
DP  - 1992 Aug
TI  - Function and evolution in the NGF family and its receptors.
PG  - 461-70
AB  - The gene family of neurotrophins includes nerve growth factor (NGF), 
      brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and 
      neurotrophin-4 (NT-4). Recently, neurotrophin-5 (NT-5), a possible mammalian 
      homologue to NT-4 described in the frog Xenopus, has been cloned in man and rat. 
      The neurotrophins stimulate survival and differentiation of a range of target 
      neurons by binding to cell surface receptors. The structure of NGF has recently 
      been clarified from crystallographic data. The similarities between the different 
      neurotrophins are substantial with the variable regions, giving specificity to 
      each of the family members, being localized to some exposed loop regions. 
      Low-affinity binding (Kd of 10(-9) M) of all tested neurotrophins is mediated via 
      a 75 K glycoprotein (LNGFR) that has been cloned and characterized. A 140 K 
      tyrosine protein kinase encoded by the proto-oncogene trk has been found to bind 
      NGF with high affinity (Kd of 10(-11) M) and to evoke the cellular neurotrophic 
      responses. In addition, a protein encoded by the trk-related gene trkB has been 
      shown to bind BDNF. Recently, a third member of the trk family, trkC, has been 
      cloned and demonstrated to function as a high-affinity receptor for NT-3. The 
      expression of trk and LNGFR mRNA are co-localized in the rat brain to the medial 
      septal nucleus and the nucleus of Broca's diagonal band containing the 
      NGF-responsive magnocellular cholinergic neurons projecting to hippocampus and 
      cerebral cortex. In sharp contrast, the pattern of expression of trkB is widely 
      spread in many areas of the cortex as well as lateral septum. The trkB protein 
      might serve general functions in large areas of the cortex. Site-directed 
      mutagenesis and expression of recombinant chimaeric neurotrophin proteins have 
      made it possible to localize a likely region for the interaction between NGF and 
      the LNGFR. This region could be altered, resulting in the total loss of LNGFR 
      binding by the mutant NGF protein without affecting the binding to the trk 
      receptor which was sufficient for the full biological activity. Cladistic 
      analysis of likely phylogenies within the neurotrophins shows BDNF and NT-4 to be 
      most closely related whereas NGF may be the sister group to NT-3, BDNF, and NT-4. 
      Neurotrophins offer obvious clinical possibilities for treatment of 
      neurodegenerative diseases.
FAU - Ebendal, T
AU  - Ebendal T
AD  - Department of Developmental Biology, Uppsala University, Sweden.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (MAS1 protein, human)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Nerve Growth Factor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Evolution
MH  - Humans
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/*physiology
MH  - Proto-Oncogene Mas
MH  - Receptors, Cell Surface/*physiology
MH  - Receptors, Nerve Growth Factor
RF  - 69
EDAT- 1992/08/01 00:00
MHDA- 1992/08/01 00:01
CRDT- 1992/08/01 00:00
PHST- 1992/08/01 00:00 [pubmed]
PHST- 1992/08/01 00:01 [medline]
PHST- 1992/08/01 00:00 [entrez]
AID - 10.1002/jnr.490320402 [doi]
PST - ppublish
SO  - J Neurosci Res. 1992 Aug;32(4):461-70. doi: 10.1002/jnr.490320402.