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Volume 271, Number 28, Issue of July 12, 1996 pp. 16753-16757
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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The HIV Nef Protein Associates with Protein Kinase C Theta

(Received for publication, March 18, 1996, and in revised form, April 23, 1996)

Bradley L. Smith , Bohdan W. Krushelnycky , Daria Mochly-Rosen and Paul Berg

From the Departments of Biochemistry and  Molecular Pharmacology, Beckman Center and Stanford University School of Medicine, Stanford, California 94305

Expression of the human immunodeficiency virus (HIV) Nef protein has been linked to both decreased cell surface expression of CD4 and an impairment of signal transduction. The recently reported association of Nef with an unidentified serine kinase provides a clue as to how Nef might exert its effects. Considering the key role of protein kinase C (PKC) in T cell activation, we investigated the possibility that Nef interacts with PKC. Our results, using two approaches for detecting interactions between Nef and PKC isozymes in Jurkat cells, show that Nef interacts preferentially with PKC. The interaction of Nef and PKC is independent of calcium, enhanced by phospholipid activators of PKC and not affected by a PKC pseudosubstrate peptide. Phorbol 12-myristate 13-acetate and phytohemagglutinin stimulation of Jurkat cells expressing Nef fails to produce the usual translocation of PKC from the cytosol to the particulate fraction; translocation of PKC and PKC was unaffected. Indeed, there appears to be a net loss of PKC in Nef-expressing cells following stimulation. The loss of PKC, which may be a result of inhibition of its binding to RACKs due to Nef binding, could contribute to the various impairments of T cell function associated with HIV infection and Nef expression.

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