Abstract：
:The c-ret protooncogene encodes Ret, the functional tyrosine kinase receptor for glial cell line-derived neurotrophic factor (GDNF). K-252b, a known protein tyrosine kinase inhibitor, has been shown earlier to inhibit the trophic activity of brain-derived neurotrophic factor on dopaminergic (DAergic) neurons and nerve growth factor on basal forebrain cholinergic neurons while potentiating neurotrophin-3 activity on central cholinergic and peripheral sensory neurons and PC12 cells. We tested whether K-252b would modulate GDNF-induced differentiation in DAergic neuron cultures. Exposure to 1 ng/ml GDNF increased dopamine (DA) uptake 80% above control, whereas treatment with 5 microM K-252b decreased the efficacy of GDNF by 60%. Concentrations of GDNF of <100 pg/ml were completely inhibited, whereas concentrations of >100 pg/ml were moderately active, between 10 and 20% above control. In addition, K-252b shifted the ED50 from 20 to 200 pg/ml. GDNF treatment increased soma size and neurite outgrowth in tyrosine hydroxylase-immunoreactive neurons. K-252b inhibited differentiation of these morphological parameters induced by GDNF. Furthermore, GDNF stimulated Ret autophosphorylation at maximal levels, whereas the inhibition of DA uptake and morphological differentiation by K-252b correlated with a significantly decreased level of Ret autophosphorylation. Therefore, K-252b is able to inhibit intracellular activities induced by GDNF on mesencephalic DAergic neurons.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Pong K,Xu RY,Beck KD,Zhang TJ,Louis JCdoi
10.1046/j.1471-4159.1997.69030986.xsubject
Has Abstractpub_date
1997-09-01 00:00:00pages
986-94issue
3eissn
0022-3042issn
1471-4159journal_volume
69pub_type
杂志文章abstract：:Homologues of the Drosophila melanogaster tweety (tty) gene are present in mammals and Caenorhabditis elegans. The encoded proteins have five predicted membrane-spanning regions and recent findings suggest that some family members may be chloride channels. Phylogenetic analysis of the tty family including novel member...
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abstract：:Niemann Pick type C (NPC1) is a rare fatal hereditary cholesterol storage disease associated with a massive Purkinje cells loss. The mechanisms leading to neurodegeneration are still poorly understood. Different laboratories pointed to hypersensitivity to cytotoxic effects of statins (HMG-CoA reductase inhibitors) in ...
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doi：10.1046/j.1471-4159.1995.65020475.x
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abstract：:PEA-15 has recently been identified as a major phosphoprotein in astrocytes and an endogenous substrate for protein kinase C. This 15-kDa protein exists under three molecular forms, an unphosphorylated form, N, and two phosphorylated forms, Pa and Pb. Antisera were raised against synthetic peptides corresponding to th...
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pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64031016.x
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64041892.x
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doi：10.1111/j.1471-4159.1981.tb00479.x
更新日期：1981-08-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb07902.x
更新日期：1982-05-01 00:00:00
abstract：:TrkA is a receptor tyrosine kinase for nerve growth factor (NGF). Recent studies indicate that NGF regulates not only activation of trkA kinase but also expression of the trkA gene. To further define NGF actions on trkA, we examined binding and signaling through trkA after both short and long intervals of NGF treatmen...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65031146.x
更新日期：1995-09-01 00:00:00
abstract：:The effect of hypoglycaemic, hypoxic, and ischaemic conditions on high-affinity neurotransmitter transport was studied in the human astrocytoma clone D384 and the human neuroblastoma clone SH-SY5Y. Both cell lines expressed a sodium-dependent glutamate/aspartate transporter. Km values for D-[3H]aspartate uptake were 6...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63020603.x
更新日期：1994-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0741711.x
更新日期：2000-04-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09751.x
更新日期：1992-02-01 00:00:00
abstract：:A wealth of evidence supports the view that conformational change of the prion protein, PrPC, into a pathogenic isoform, PrPSc, is the hallmark of sporadic, infectious, and inherited forms of prion disease. Although the central role played by PrPSc in the pathogenesis of prion disease is appreciated, the cellular mech...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01819.x
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journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
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pub_type： 杂志文章,评审
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journal_title：Journal of neurochemistry
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doi：10.1046/j.1471-4159.1994.62031039.x
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更新日期：2005-09-01 00:00:00
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doi：10.1046/j.1471-4159.1998.70020835.x
更新日期：1998-02-01 00:00:00
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更新日期：2006-10-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb11296.x
更新日期：1983-02-01 00:00:00
abstract：:Currently, the underlying mechanisms and the specific cell types associated with Japanese encephalitis-associated leukocyte trafficking are not understood. Brain microvascular endothelial cells represent a functional barrier and could play key roles in leukocyte central nervous system trafficking. We found that cultur...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2012.07889.x
更新日期：2012-10-01 00:00:00
abstract：:Mutations in the presenilin-1 (PS-1) and presenilin-2 (PS-2) genes account for the majority of cases of early-onset familial Alzheimer's disease (AD). Alternative splicing forms of the PS-1 and PS-2 gene products have previously been reported in fibroblast and brain tissue from both familial and sporadic AD patients, ...
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pub_type： 杂志文章
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更新日期：1999-06-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：1997-01-01 00:00:00
abstract：:This laboratory has previously demonstrated that the mu-selective opiate receptor agonist sufentanil can produce a naloxone-reversible increase or decrease in the stimulated formation of cyclic AMP (cAMP) in the myenteric plexus, depending on the concentration of opioid used. On the basis of these results, it was sugg...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64031102.x
更新日期：1995-03-01 00:00:00
abstract：:The NMDA receptor has recently been found to be phosphorylated on tyrosine. To assess the possible connection between tyrosine phosphorylation of the NMDA receptor and signaling pathways in the postsynaptic cell, we have investigated the relationship between tyrosine phosphorylation and the binding of NMDA receptor su...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.69020623.x
更新日期：1997-08-01 00:00:00
abstract：:Exhaustive in vitro dephosphorylation of porcine neurofilaments (NFs) by alkaline or acid phosphatase did not cause a dissociation of the 210-kD (NF-H), 160-kD (NF-M), or 70-kD (NF-L) subunits and had no effect on the reassembly of NFs from urea or guanidine solution. Electron microscopy revealed that the NFs reassemb...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb04526.x
更新日期：1986-08-01 00:00:00
