Specific Interaction of the Human Immunodeficiency Virus Tat Proteins With a Cellular Protein Kinase

Virology. 1993 Dec;197(2):601-8. doi: 10.1006/viro.1993.1634.

Abstract

The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) Tat proteins are related transcriptional activators whose effects are likely to be mediated by a cellular factor. Using an in vitro kinase assay, we have shown that the Tat protein of HIV-2 and the activation domain of the Tat protein of HIV-1 specifically bind to a cellular protein kinase. Mutations in Tat that abolish transactivation activity in vivo abrogate the ability of the mutants to bind to the kinase in vitro. This is the first demonstration of a cellular factor that binds to Tat that is specific for a functional activation domain of Tat and that displays a biochemical activity. Additionally, we show that the Tat protein of HIV-2 serves as a substrate of the kinase in vitro. Consistent with the in vitro results, the Tat protein of HIV-2 interacts with a cellular kinase in HIV-2 Tat-transfected cells and is phosphorylated in vivo. These results suggest that a cellular serine/threonine kinase may act as a mediator of Tat function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA Mutational Analysis
  • Gene Expression Regulation, Viral
  • Gene Products, tat / genetics
  • Gene Products, tat / metabolism*
  • HIV-2 / metabolism*
  • Humans
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity
  • Transcription, Genetic
  • Transcriptional Activation
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, tat
  • Recombinant Fusion Proteins
  • tat Gene Products, Human Immunodeficiency Virus
  • Protein-Serine-Threonine Kinases