Protein kinase C δ (PKCδ) inhibits the expression of glutamine synthetase in glial cells via the PKCδ regulatory domain and its tyrosine phosphorylation

Chaya Brodie, Krisztina Bogi, Peter Acs, Patricia S. Lorenzo, Lindsey Baskin, Peter M. Blumberg

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36 Scopus citations

Abstract

Protein kinase C (PKC) plays an important role in the proliferation and differentiation of glial cells. In a recent study we found that overexpression of PKCδ reduced the expression of the astrocytic marker glutamine synthetase (GS). In this study we explored the mechanisms involved in the inhibitory effect of PKCδ on the expression of glutamine synthetase. Using PKC chimeras we first examined the role of the catalytic and regulatory domains of PKCδ on the expression of glutamine synthetase. We found that cells stably transfected with chimeras between the regulatory domain of PKCδ and the catalytic domains of PKCα or ε inhibited the expression of GS, similar to the inhibition exerted by overexpression of PKCδ itself. In contrast, no significant effects were observed in cells transfected with the reciprocal PKC chimeras between the regulatory domains of PKCα or ε and the catalytic domain of PKCδ. PKCδ has been shown to undergo tyrosine phosphorylation in response to various activators. Tyrosine phosphorylation of PKCδ in response to phorbol 12-myristate 13-acetate and platelet-derived growth factor occurred only in chimeras which contained the PKCδ regulatory domain. Cells transfected with a PKCδ mutant (PKCδ5), in which the five putative tyrosine phosphorylation sites were mutated to phenylalanine, showed markedly diminished tyrosine phosphorylation in response to phorbol 12- myristate 13-acetate and platelet-derived growth factor and normal levels of GS. Our results indicate that the regulatory domain of PKCδ mediates the inhibitory effect of this isoform on the expression of GS. Phosphorylation of PKCδ on tyrosine residues in the regulatory domain is implicated in this inhibitory effect.

Original languageEnglish
Pages (from-to)30713-30718
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number46
DOIs
StatePublished - 13 Nov 1998

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