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Depression of Neuronal Protein Synthesis Initiation by Protein Tyrosine Kinase Inhibitors

Hu, Bing Ren ; Ou Yang, Yi Bing and Wieloch, Tadeusz LU (1993) In Journal of Neurochemistry 61(5). p.1789-1794
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... (More)

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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author
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organization
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type
Contribution to journal
publication status
published
subject
keywords
eceptor, euronal deat, rotein synthesi, rowth factors, tress, Tyrosine kinas, ukaryotic initiation facto
in
Journal of Neurochemistry
volume
61
issue
5
pages
6 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:0027421352
  • pmid:8228995
ISSN
0022-3042
DOI
10.1111/j.1471-4159.1993.tb09817.x
language
English
LU publication?
yes
id
5a3a48c8-05b4-4590-894f-44174fa6bf56
date added to LUP
2019-06-13 16:16:03
date last changed
2024-01-01 10:16:52
@article{5a3a48c8-05b4-4590-894f-44174fa6bf56,
  abstract     = {{<p>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 &gt;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.</p>}},
  author       = {{Hu, Bing Ren and Ou Yang, Yi Bing and Wieloch, Tadeusz}},
  issn         = {{0022-3042}},
  keywords     = {{eceptor; euronal deat; rotein synthesi; rowth factors; tress; Tyrosine kinas; ukaryotic initiation facto}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{5}},
  pages        = {{1789--1794}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Neurochemistry}},
  title        = {{Depression of Neuronal Protein Synthesis Initiation by Protein Tyrosine Kinase Inhibitors}},
  url          = {{http://dx.doi.org/10.1111/j.1471-4159.1993.tb09817.x}},
  doi          = {{10.1111/j.1471-4159.1993.tb09817.x}},
  volume       = {{61}},
  year         = {{1993}},
}