Differential action of nerve growth factor and phorbol ester TPA on rat synaptosomal PKC isoenzymes

Carles Gil, Patricia Pelliccioni, Emili Itarte, José Aguilera

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The subcellular redistribution of protein kinase C family members (α, β, γ, δ, ε and ζ isoforms) was examined in response to treatment with 12-O-tetradecanoyl-phorbol-13 acetate (TPA) or nerve growth factor (NGF) in a synaptosomal-enriched P2 fraction from rat brain. Treatment with TPA affected members of the classical-PKC family (α, β and γ), resulting in a final loss of total protein of each isoenzyme. The kinetics of changes of members of the novel-PKC family are different, the δ isoform being translocated, but not down-regulated, while the ε isoform showing only a slight diminishing of immunoreactivity in the soluble and particulate fractions. The atypical-PKC ζ isoform was not translocated in response to TPA. Incubation with NGF induced a loss of immunoreactivity of the cytosolic α, β and ε isoforms, but the membrane fractions of these isoforms were not appreciably affected. In contrast, a marked translocation from cytosol to membrane was observed in the case of the γ and δ isoforms. The ζ isoform presented a slight translocation from the particulate fraction to the soluble fraction. Thus, the results show that the effects of TPA and NGF on PKC isoforms are not coincident in synaptosomes, the δ isoform being activated and not down-regulated by both treatments, whereas the γ isoform is only down-regulated in the case of TPA, but presents sustained translocation with NGF, indicating that PKC isoform-specific degradation pathways exist in synaptic terminals. The effects of NGF on PKC isoforms coexist with an increase in NGF-induced polyphosphoinositide hydrolysis, suggesting the participation of phospholipases. Copyright (C) 1999 Elsevier Science Ltd.
Original languageEnglish
Pages (from-to)281-291
JournalNeurochemistry International
Issue number4
Publication statusPublished - 1 Oct 1999


  • Isoforms
  • Nerve growth factor
  • Phospholipid hydrolysis
  • Protein kinase C
  • Rat brain
  • Synaptosomes


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