Depression of Neuronal Protein Synthesis Initiation by Protein Tyrosine Kinase Inhibitors
(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
- Hu, Bing Ren ; Ou Yang, Yi Bing and Wieloch, Tadeusz LU
- organization
- publishing date
- 1993-01-01
- 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
-
- pmid:8228995
- scopus:0027421352
- 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 >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}}, }