Depression of Neuronal Protein Synthesis Initiation by Protein Tyrosine Kinase Inhibitors

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Lund University
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Läkemedelskemi

Nyckelord

Originalspråkengelska
Sidor (från-till)1789-1794
Antal sidor6
TidskriftJournal of Neurochemistry
Volym61
Utgåva nummer5
StatusPublished - 1993 jan 1
PublikationskategoriForskning
Peer review utfördJa