A Quantitative Bioassay for Nerve Growth Factor,Using PC12 Clones Expressing Different Levels of trkA Receptors

2002 ◽  
Vol 18 (3) ◽  
pp. 251-264 ◽  
Author(s):  
Itzhak Katzir ◽  
Jashovam Shani ◽  
Keren Regev ◽  
Dalia Shabashov ◽  
Philip Lazarovici
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Nerve Growth ◽  
Trka Receptors ◽  
Different Levels ◽  
Quantitative Bioassay

scholarly journals Small Peptide Mimics of Nerve Growth Factor Bind TrkA Receptors and Affect Biological Responses

1995 ◽  
Vol 270 (12) ◽  
pp. 6564-6569 ◽  
Author(s):  
Lynne LeSauteur ◽  
Ling Wei ◽  
Bernard F. Gibbs ◽  
H. Uri Saragovi
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Small Peptide ◽  
Peptide Mimics ◽  
Nerve Growth ◽  
Biological Responses ◽  
Trka Receptors

scholarly journals PC12nnr5 cells expressing TrkA receptors undergo morphological but not cholinergic phenotypic differentiation in response to nerve growth factor

2002 ◽  
Vol 80 (3) ◽  
pp. 501-511 ◽  
Author(s):  
Jacqueline C. Baskey ◽  
Bettina E. Kalisch ◽  
Wanda L. Davis ◽  
Susan O. Meakin ◽  
R. Jane Rylett
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Phenotypic Differentiation ◽  
Nerve Growth ◽  
Trka Receptors

scholarly journals Nerve Growth Factor Induces Apoptosis in Human Medulloblastoma Cell Lines that Express TrkA Receptors

1997 ◽  
Vol 17 (2) ◽  
pp. 530-542 ◽  
Author(s):  
Yoshihiro Muragaki ◽  
Thomas T. Chou ◽  
David R. Kaplan ◽  
John Q. Trojanowski ◽  
Virginia M.-Y. Lee
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cell Lines ◽  
Nerve Growth ◽  
Medulloblastoma Cell ◽  
Trka Receptors ◽  
Human Medulloblastoma ◽  
Medulloblastoma Cell Lines

scholarly journals A Pro-Nerve Growth Factor (proNGF) and NGF Binding Protein, α2-Macroglobulin, Differentially Regulates p75 and TrkA Receptors and Is Relevant to NeurodegenerationEx VivoandIn Vivo

2015 ◽  
Vol 35 (19) ◽  
pp. 3396-3408 ◽  
Author(s):  
Pablo F. Barcelona ◽  
H. Uri Saragovi
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Ex Vivo ◽  
Neurotrophin Receptor ◽  
Tyrosine Kinase Receptor ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Nerve Growth ◽  
Trka Receptors

Nerve growth factor (NGF) is generated from a precursor, proNGF, that is proteolytically processed. NGF preferentially binds a trophic tyrosine kinase receptor, TrkA, while proNGF binds a neurotrophin receptor (NTR), p75NTR, that can have neurotoxic activity. Previously, we along with others showed that the soluble protein α2-macroglobulin (α2M) is neurotoxic. Toxicity is due in part to α2M binding to NGF and inhibiting trophic activity, presumably by preventing NGF binding to TrkA. However, the mechanisms remained unclear. Here, we showex vivoandin vivothree mechanisms for α2M neurotoxicity. First, unexpectedly the α2M-NGF complexes do bind TrkA receptors but do not induce TrkA dimerization or activation, resulting in deficient trophic support. Second, α2M makes stable complexes with proNGF, conveying resistance to proteolysis that results in more proNGF and less NGF. Third, α2M-proNGF complexes bind p75NTRand are more potent agonists than free proNGF, inducing tumor necrosis factor alpha (TNF-α) production. Hence, α2M regulates proNGF/p75NTRpositively and mature NGF/TrkA negatively, causing neuronal deathex vivo. These three mechanisms are operativein vivo, and α2M causes neurodegeneration in a p75NTR- and proNGF-dependent manner. α2M could be exploited as a therapeutic target, or as a modifier of neurotrophin signals.

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