| 1. |
- Hu, Bing Ren, et al.
(författare)
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Depression of Neuronal Protein Synthesis Initiation by Protein Tyrosine Kinase Inhibitors
- 1993
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 61:5, s. 1789-1794
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Tidskriftsartikel (refereegranskat)abstract
- Abstract— Growth factors stimulate cellular protein synthesis, but the intracellular signaling mechanisms that regulate initiation of mRNA translation in neurons have not been clarified. A rate‐limiting step in the initiation of protein synthesis is the formation of the ternary complex among GTP, eukaryotic initiation factor 2 (elF‐2), and the initiator tRNA. Here we report that genistein, a specific tyrosine kinase inhibitor, decreases tyrosine kinase activity and the content of phosphotyrosine proteins in cultured primary cortical neurons. Genistein inhibits protein synthesis by >80% in a dose‐dependent manner (10–80 μg/ml) and concurrently decreases ternary complex formation by 60%. At the doses investigated, genistein depresses tyrosine kinase activity and concomitantly stimulates PKC activity. We propose that a protein tyrosine kinase participates in the initiation of protein synthesis in neurons, by affecting the activity of elF‐2 directly or through a protein kinase cascade.
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| 2. |
- Hu, Bing Ren, et al.
(författare)
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Heat-shock inhibits protein synthesis and eIF-2 activity in cultured cortical neurons
- 1993
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Ingår i: Neurochemical Research. - 0364-3190. ; 18:9, s. 1003-1007
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Tidskriftsartikel (refereegranskat)abstract
- Stress, such as heat-shock, hypoxia and hypoglycemia, inhibits the initiation of protein synthesis. The effects of heat-shock on protein synthesis, eucaryotic initiation factor 2 (eIF-2) activity, protein kinase C (PKC), and casein kinase II (CKII) activities were studied in primary cortical neuronal cultures. In neurons exposed to heat-shock at 44°C for 20 min, protein synthesis is inhibited by more than 80%, and is accompanied by a 60% decrease in eIF-2 activity. Steady state PKC and CK II activities were not affected by heat-shock. Vanadate (200 μM), a protein phosphotyrosine phosphatase inhibitor, partially prevented the depression of eIF-2 activity during heat-shock, and increased CKII activity by 90%. In contrast, staurosporine (62nM), a protein kinase C inhibitor, did not affect eIF-2 activity. We conclude that heat-shock causes a change in the phosphorylation/ dephosphorylation of regulatory proteins leading to a depressed eIF-2 activity and protein synthesis in neurons.
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