A HERPESVIRUS SAIMIRI MEMBRANE-PROTEIN REQUIRED FOR INTERLEUKIN-2 INDEPENDENCE FORMS A STABLE COMPLEX WITH P56(LCK)

ORF-2, a 32-kDa viral protein expressed by herpesvirus saimiri-transfo rmed lymphocytes, is essential for transformation and is expressed on the plasma membrane of transformed cells. The current work now shows t hat most (approximately 80%) of ORF-2 resides in the cytoplasm, white only a small portion protrudes from the cell surface. Expressed as a g lutathione S-transferase fusion protein, ORF-2 was found to interact w ith a 56-kDa cellular protein in untransformed, herpesvirus saimiri-tr ansformed, and Jurkat lymphocytes. Microsequencing proved that this pr otein is the lymphocyte-specific tyrosine protein kinase p56(lck). Two regions of ORF-2 were found to be required for p55(lck) interaction. Current evidence suggests that the interaction of ORF-2 with p56(lck) plays a keg rot in the specific transformation of T lymphocytes to an interleukin-2-independent phenotype.