The herpesvirus saimiri tip484 and tip488 proteins both stimulate lck tyrosine protein kinase activity in vivo and in vitro.
Herpesvirus saimiri (HVS) of subgroup C efficiently induces leukemia in New World primates and transforms human lymphocytes. The viral tyrosine kinase interacting protein (Tip) binds to the tyrosine protein kinase Lck and is essential for transformation. Understanding how Tip modulates Lck activity is important for elucidating the mechanism of herpesvirus saimiri leukemogenesis. However, there are reports suggesting that whereas the Tip protein of HVS strain 484 stimulates the activity of Lck, the Tip protein of HVS strain 488 inhibits Lck. To determine whether these two divergent Tip proteins have opposite effects on Lck activity, we compared them in parallel. We found that both Tip proteins stimulated Lck kinase activity in vivo and in vitro and that both stimulated NF-AT- and STAT3-dependent transcription in T cells. Our data support the model that HVS infection increases the activity of Lck through the action of Tip.
Kjellen
Peter
P
Molecular Cell and Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Amdjadi
Kambiz
K
Lund
Troy C
TC
Medveczky
Peter G
PG
Sefton
Bartholomew M
BM
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D006567:Herpesvirus 2, Saimiriine; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)