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Depression of Neuronal Protein Synthesis Initiation by Protein Tyrosine Kinase Inhibitors
Author(s) -
Hu Bing Ren,
Ou Yang Yi Bing,
Wieloch Tadeusz
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb09817.x
Subject(s) - genistein , protein kinase c , proto oncogene tyrosine protein kinase src , tyrosine kinase , protein tyrosine phosphatase , mitogen activated protein kinase kinase , receptor tyrosine kinase , microbiology and biotechnology , ask1 , map2k7 , protein kinase a , biology , cyclin dependent kinase 2 , tyrosine , chemistry , biochemistry , signal transduction , phosphorylation , endocrinology
— 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.