A herpesvirus saimiri membrane protein required for interleukin-2 independence forms a stable complex with p56lck.
ORF-2, a 32-kDa viral protein expressed by herpesvirus saimiri-transformed lymphocytes, is essential for transformation and is expressed on the plasma membrane of transformed cells. The current work now shows that most (approximately 80%) of ORF-2 resides in the cytoplasm, while only a small portion protrudes from the cell surface. Expressed as a glutathione S-transferase fusion protein, ORF-2 was found to interact with a 56-kDa cellular protein in untransformed, herpesvirus saimiri-transformed, and Jurkat lymphocytes. Microsequencing proved that this protein is the lymphocyte-specific tyrosine protein kinase p56lck. Two regions of ORF-2 were found to be required for p56lck interaction. Current evidence suggests that the interaction of ORF-2 with p56lck plays a key role in the specific transformation of T lymphocytes to an interleukin-2-independent phenotype.
Department of Microbiology and Immunology, University of South Florida, Tampa 33612-4799, USA.
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Lund
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Medveczky
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Neame
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Medveczky
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase