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Extracellular HIV-1 Tat Protein Induces a Rapid and Selective Activation of Protein Kinase C (PKC)-α, -ϵ, and -ζ Isoforms in PC12 Cells

https://doi.org/10.1006/bbrc.1997.7877Get rights and content

Abstract

The addition in culture of extracellular HIV-1 Tat protein (0.1-1 nM) to PC12 cells induced a rapid increase of the bulk protein kinase C (PKC) catalytic activity. Among various PKC isoforms (α, βI, βII, δ, ϵ, η, θ, and ζ) expressed in PC12 cells, Tat selectively stimulated α, ϵ, and ζ, as judged by activities in immunoprecipitates. Activation of these isoforms was suppressed by the tyrosine kinase inhibitor genistein. Moreover, PKC-ζ showed the fastest kinetics of activation in response to Tat, but PKC-α and PKC-ϵ showed the highest levels of activation. PKC-α activation was accompanied by a rise of intracellular IP3, while the PI 3-kinase inhibitors wortmannin and LY294002 suppressed PKC-ϵ activation. Taken together, these findings demonstrate that extracellular Tat shows a cytokine-like activity in PC12 cells, being able to trigger an intracellular signalling cascade which involves PKC-α, -ϵ, and -ζ.

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