TAT PROTEIN FROM HIV-1 ACTIVATES MAP KINASE IN GRANULAR NEURONS AND GLIAL-CELLS FROM RAT CEREBELLUM

We have investigated the effect of extracellularly applied Tat protein of the human immunodeficiency virus type 1 (HIV-1) on tyrosine phosph orylation processes, which represent a major signal transduction pathw ay of cells of the central nervous system. Primary cultures of rat cer ebellar astrocytes or granule cells were incubated with synthetic Tat (10 ng/ml) for various periods of time and analyzed for their phosphot yrosine content by Western blotting, In both types of cultures Tat was able to induce the phosphorylation of mitogen-activated protein kinas e (MAP kinase) on tyrosine residues, although with different kinetics and isoform specificity. In addition, in neuronal cells, but not in as trocytes, Tat increased the phosphotyrosine content of She, a protein involved in signal transduction downstream of receptor tyrosine kinase activation, This study shows that Tat applied extracellularly is able to induce the generation of intracellular signals in neuronal as well as glial cells. (C) 1997 Academic Press.