scholarly journals Glial Cell Line-Derived Neurotrophic Factor Family Members Sensitize Nociceptors In Vitro and Produce Thermal Hyperalgesia In Vivo

2006 ◽  
Vol 26 (33) ◽  
pp. 8588-8599 ◽  
Author(s):  
S. A. Malin ◽  
D. C. Molliver ◽  
H. R. Koerber ◽  
P. Cornuet ◽  
R. Frye ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Family Members ◽  
Thermal Hyperalgesia

scholarly journals A Novel Activating Mutation in the RET Tyrosine Kinase Domain Mediates Neoplastic Transformation

2006 ◽  
Vol 20 (7) ◽  
pp. 1633-1643 ◽  
Author(s):  
Aaron Cranston ◽  
Cristiana Carniti ◽  
Sam Martin ◽  
Piera Mondellini ◽  
Yvette Hooks ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Functional Characterization ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Exogenous Substrate

Abstract We report the finding of a novel missense mutation at codon 833 in the tyrosine kinase of the RET proto-oncogene in a patient with a carcinoma of the thyroid. In vitro experiments demonstrate that the R833C mutation induces transformed foci only when present in the long 3′ splice isoform and, in keeping with a model in which the receptor has to dimerize to be completely activated, glial cell line-derived neurotrophic factor stimulation leads the RETR833C receptor to a higher level of activation. Tyrosine kinase assays show that the RETR833C long isoform has weak intrinsic kinase activity and phosphorylation of an exogenous substrate is not elevated even in the presence of glial cell line-derived neurotrophic factor. Furthermore, the R833C mutation is capable of sustaining the transformed phenotype in vivo but does not confer upon the transformed cells the ability to degrade the basement membrane in a manner analogous to metastasis. Our functional characterization of the R833C substitution suggests that, like the V804M and S891A mutations, this tyrosine kinase mutation confers a weak activating potential upon RET. This is the first report demonstrating that the introduction of an intracellular cysteine can activate RET. However, this does not occur via dimerization in a manner analogous to the extracellular cysteine mutants.

scholarly journals Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 280
Author(s):  
Laura Bizzozero ◽  
Margherita Pergolizzi ◽  
Davide Pascal ◽  
Elena Maldi ◽  
Giulia Villari ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Glial Cell ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Neurotrophic Factor ◽  
Regulatory Protein ◽  
Cancer Cell Invasion

Many nervous proteins are expressed in cancer cells. In this report, we asked whether the synaptic protein neuroligin 1 (NLGN1) was expressed by prostatic and pancreatic carcinomas; in addition, given the tendency of these tumors to interact with nerves, we asked whether NLGN1 played a role in this process. Through immunohistochemistry on human tissue microarrays, we showed that NLGN1 is expressed by prostatic and pancreatic cancer tissues in discrete stages and tumor districts. Next, we performed in vitro and in vivo assays, demonstrating that NLGN1 promotes cancer cell invasion and migration along nerves. Because of the established role of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) in tumor–nerve interactions, we assessed a potential NLGN1–GDNF cooperation. We found that blocking GDNF activity with a specific antibody completely inhibited NLGN1-induced in vitro cancer cell invasion of nerves. Finally, we demonstrated that, in the presence of NLGN1, GDNF markedly activates cofilin, a cytoskeletal regulatory protein, altering filopodia dynamics. In conclusion, our data further prove the existence of a molecular and functional cross-talk between the nervous system and cancer cells. NLGN1 was shown here to function along one of the most represented neurotrophic factors in the nerve microenvironment, possibly opening new therapeutic avenues.

Extracellular poly(ADP-ribose) is a neurotrophic signal that upregulates glial cell line-derived neurotrophic factor (GDNF) levels in vitro and in vivo

2017 ◽  
Vol 484 (2) ◽  
pp. 385-389 ◽  
Author(s):  
Hidemitsu Nakajima ◽  
Masanori Itakura ◽  
Keishi Sato ◽  
Sunao Nakamura ◽  
Yasu-Taka Azuma ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor

scholarly journals Glial Cell Line–Derived Neurotrophic Factor Receptor Rearranged During Transfection Agonist Supports Dopamine Neurons In Vitro and Enhances Dopamine Release In Vivo

2019 ◽  
Vol 35 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Arun Kumar Mahato ◽  
Jaakko Kopra ◽  
Juho‐Matti Renko ◽  
Tanel Visnapuu ◽  
Ilari Korhonen ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopamine Release ◽  
Dopamine Neurons

Glial Cell Line-Derived Neurotrophic Factor Augments Midbrain Dopaminergic Circuits In Vivo

1995 ◽  
pp. 401-415
Author(s):  
BARRY J. HOFFER ◽  
JOHN HUDSON ◽  
GREG A. GERHARDT ◽  
MICHAEL A. HENRY ◽  
ALEX HOFFMAN ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor

scholarly journals The major determinant of the heparin binding of glial cell-line-derived neurotrophic factor is near the N-terminus and is dispensable for receptor binding

2007 ◽  
Vol 404 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Ivan Alfano ◽  
Parvez Vora ◽  
Rosemary S. Mummery ◽  
Barbara Mulloy ◽  
Christopher C. Rider
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Transforming Growth Factor ◽  
Basic Amino Acid ◽  
Transforming Growth Factor Β ◽  
Heparin Binding ◽  
Binding Sequence

GDNF (glial cell-line-derived neurotrophic factor), and the closely related cytokines artemin and neurturin, bind strongly to heparin. Deletion of a basic amino-acid-rich sequence of 16 residues N-terminal to the first cysteine of the transforming growth factor β domain of GDNF results in a marked reduction in heparin binding, whereas removal of a neighbouring sequence, and replacement of pairs of other basic residues with alanine had no effect. The heparin-binding sequence is quite distinct from the binding site for the high affinity GDNF polypeptide receptor, GFRα1 (GDNF family receptor α1), and heparin-bound GDNF is able to bind GFRα1 simultaneously. The heparin-binding sequence of GDNF is dispensable both for GFRα1 binding, and for activity for in vitro neurite outgrowth assay. Surprisingly, the observed inhibition of GDNF bioactivity with the wild-type protein in this assay was still found with the deletion mutant lacking the heparin-binding sequence. Heparin neither inhibits nor potentiates GDNF–GFRα1 interaction, and the extracellular domain of GFRα1 does not bind to heparin itself, precluding heparin cross-bridging of cytokine and receptor polypeptides. The role of heparin and heparan sulfate in GDNF signalling remains unclear, but the present study indicates that it does not occur in the first step of the pathway, namely GDNF–GFRα1 engagement.

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