Activation of S6 kinase activity in astrocytes by insulin, somatomedin C and TPA

Abstract

Treatment of cultured astrocytes from 2‐day‐old rat cerebral hemispheres with insulin or somatomedin C (IGF1) promoted a rapid activation of a cytosolic protein kinase which phosphorylates ribosomal protein S6. Phosphorylation of substrates currently used for protein kinase assays (histone H2B and phosvitin) was not stimulated. Neither the cyclic AMP‐dependent protein kinase activity nor that of protein kinase C was modified. Treatment of these astrocytes with TPA also promoted a rapid increase in S6 kinase activity in the cytosolic fraction. Simultaneously, protein kinase C disappeared from the cytosol. Neither cyclic AMP‐dependent protein kinase activity nor phosvitin kinase activity was modified. The effects of insulin, IGF1 and TPA were also observed in the presence of cycloheximide. Cycloheximide also potentiated their effects. These data indicate that S6 kinase activity in astrocytes is promoted from a pre‐existing molecule via the tyrosine kinase‐insulin receptor and suggest that protein kinase C is implicated in the process.