Structure and developmental expression of the chicken NGF receptor

Heuer, Josef G.; Fatemie-Nainie, S.; Wheeler, Esther F.; Bothwell, Mark

doi:10.1016/0012-1606(90)90255-h

Cited by 122 publications

(69 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These residues are found on the third and fourth subdomains of NTR, consistent with deletion studies and the location of ligand-blocking monoclonal antibody epitopes (Welcher et al, 1991;Baldwin et al, 1992;Baldwin & Shooter, 1994). NTRs from three species have been sequenced (Johnson et al, 1986;Radeke et al, 1987;Large et al, 1989;Heuer et al, 1990). Predicted binding site residues Thr 91, Glu 95, Arg 150, Glu 15 1, and Cys 152 are either identical or have very conservative replacements in human, rat, and chicken receptors.…”

Section: Analysis Of Receptor-ligand Interactions By Molecular Dockingmentioning

confidence: 99%

Modeled structure of the 75-kDa neurotrophin receptor

Chapman

Kuntz

1995

Protein Sci.

View full text Add to dashboard Cite

Motifs in ligand-binding domains of the neurotrophin (NTR) and lymphotoxin (TNFR-I) receptors define a family of receptors that mediates programmed cell death. We have explored relationships of architecture and function in this family through a molecular model of NTR, also called p75NGFR or LANR. Modeling by homology took advantage of four modular subdomains in the crystal structure of TNFR-I that also occur in NTR. Hypothetical complexes between the model and a ligand structure (for nerve growth factor, NGF) were then examined using docking software. NTR appears to bind in the dimer interface of NGF, making two sets of contacts. NTR subdomains 111 and IV provide the ligand-contact surfaces, in contrast to TNFR, in which subdomains 11 and III contact TNF-6. NTR subdomain I1 appears to have been evolutionarily modified, potentially contributing to an interface between receptor subunits. These and other specific predictions of the model will require experimental confirmation.

show abstract

Section: Analysis Of Receptor-ligand Interactions By Molecular Dockingmentioning

confidence: 99%

Modeled structure of the 75-kDa neurotrophin receptor

Chapman

Kuntz

1995

Protein Sci.

View full text Add to dashboard Cite

show abstract

“…During development, mesenchymal cells, presumably fibroblasts, located in the axilla and pelvis and within developing limb buds express very high levels of p75 NTR (Heuer et al, 1990a;Heuer et al, 1990b;Wheeler and Bothwell, 1992). Mesenchymal expression of p75 NTR is also observed within several developing organs, including kidney, lung and testes, the developing inner ear and hair follicles (Byers et al, 1990;von-Bartheld et al, 1991;Wheeler and Bothwell, 1992).…”

Section: P75mentioning

confidence: 99%

p75NTR: A study in contrasts

Barker

1998

Cell Death Differ

130

View full text Add to dashboard Cite

The p75 neurotrophin receptor (p75 NTR ) and trkA, trkB and trkC mediate the physiological effects of the neurotrophins. The trk receptors are responsible for the stereotypical survival and growth properties of the neurotrophins but defining the physiological function of the p75 NTR has proven difficult. The p75 NTR binds each of the neurotrophins with low nanomolar affinity whereas the three trk receptors show strong binding preferences for individual neurotrophins; in some cell types, p75NTR is the only neurotrophin receptor whereas in others it is co-expressed with the trks. The analysis of p75 NTR function has been complicated by the fact that the predominant physiological role of p75 NTR changes dramatically depending on cell context. Available data suggests that in cells where p75 NTR is co-expressed with trk receptors, p75 NTR functionally collaborates with the trks to either enhance responses to preferred trk ligands, to reduce neurotrophin-mediated trk receptor activation resulting from non-preferred ligands or to facilitate apoptosis resulting from neurotrophin withdrawal. In cells lacking trk expression, p75 NTR can act autonomously to activate ligand-dependent signaling cascades that may in some circumstances result in apoptosis but probably not through pathways utilized by its apoptotic brethren in the TNF receptor superfamily. Potential mechanisms for each of these functions of p75 NTR are considered and the physiological implications of this unique signaling system are discussed.

show abstract

“…One receptor for NGF (designated the low-affinity p75NTR) may function as a common binding subunit for the various members of the neurotrophin family (Bothwell, 1991). The low-affinity form of NGF receptor, p75NTR, is expressed during normal embryogenesis in a variety of tissues not known to respond to NGF or other neurotrophins, including the testis, muscle anlage and somites, skin mesenchyme, and kidney (Bothwell, 1990;Heuer et al, 1990;Persson et al, 1990;Wyatt et al, 1990;Sariola et al, 1991). The expression of p75NTR in these nonresponsive tissues raises the possibility that this receptor may participate in some more general yet unknown embryonic role (Bothwell, 1990).…”

Section: Zymographic Analysis Of Secreted Proteinasesmentioning

confidence: 99%

Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trkA.

Herrmann

Menter

Hamada

et al. 1993

MBoC

117

View full text Add to dashboard Cite

Although overexpression of the low-affinity p75 neurotrophin receptor (p75NTh) is frequently associated with advanced stages of human melanoma progression, the functional significance of this finding is unknown. We examined whether the degree of cell surface expression of p75NTR in human melanoma cell variants determines their extent of invasion stimulated by nerve growth factor (NGF). Treatment of MeWo melanoma cells or a metastatic spontaneous wheat germ agglutinin-resistant variant subline (70W) of MeWo cells with 2.5S NGF resulted in a dose-dependent enhancement of invasion through a reconstituted basement membrane. This effect was most pronounced with the 70W subline that exhibits brain-metastasizing potential in nude mice but was not found with a poorly metastatic MeWo variant subline (3S5). The expression of p75NTR as determined by Northern blotting and immunoprecipitation analysis of 1251I-labeled cell surface proteins correlated with NGFstimulated invasion. The MeWo melanoma sublines used in this study did not express pl4OPrt°otr" mRNA or any p140Proto-trk variant transcripts including p70tr`as determined by Northern analysis and RT-PCR analysis. Thus, these melanoma cells would not be expected to form functional p75-p140 heterodimers or p140-p140 homodimers capable of transducing an NGF-generated signal to pl4OProto-tr cytoplasmic substrates. These cells did express authentic pl45trkc transcripts. However, NGF did not catalytically activate pl45t receptors via increased tyrosine phosphorylation as would be expected if pl45trkc participated in the signaling established by NGF. Furthermore, a NGF-stimulated wurineanalogue-sensitive kinase activity was found to coimmunoprecipitate with p75N . This p75 -associated kinase may coordinate initial signaling events evoked by p75NTR ligand interaction. Addition of 2.5S NGF, at concentrations that should saturate cell surface p75NTR, to matrix-adherent cultures of human MeWo and 70W but not 3S5 melanoma cells suppressed the expression of 92-kDa type IV collagenase and stimulated the production of 72-kDa type IV collagenase in its fully active 68-kDa form. In the absence of pl40Proto-trkA, the matrix-dependent effects of NGF on metalloproteinase expression of brain-metastatic 70W melanoma cells suggest a signaling role for the low-affinity melanoma p75NTR receptor and its associated purine-analogue-sensitive kinase in signaling enhanced matrix penetration of NGF-rich stromal microenvironments such as the brain.

show abstract

Structure and developmental expression of the chicken NGF receptor

Cited by 122 publications

References 40 publications

Modeled structure of the 75-kDa neurotrophin receptor

Modeled structure of the 75-kDa neurotrophin receptor

p75NTR: A study in contrasts

Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trkA.

Contact Info

Product

Resources

About