An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase.
Epstein-Barr virus (EBV) encodes two integral membrane proteins in latently infected growth-transformed cells. One of these, LMP1, can transform rodent fibroblasts and induce markers of B-lymphocyte activation. The second, LMP2, colocalizes with LMP1 in a constitutive patch in the EBV-transformed B-lymphocyte plasma membrane. The experiments reported here demonstrate that LMP2 may biochemically interact with LMP1 and that LMP2 closely associates with and is an important substrate for a B-lymphocyte tyrosine kinase in EBV-transformed B lymphocytes or in B-lymphoma cells in which LMP2 is expressed by gene transfer. LMP2 is also serine and threonine phosphorylated. LMP2 localizes to a peripheral membrane (presumably plasma membrane) patch in transfected B-lymphoma cells and colocalizes with much of the cellular tyrosine-phosphorylated proteins. LMP2 undergoes tyrosine phosphorylation in anti-LMP2 or antiphosphotyrosine immunoprecipitates from transfected B-lymphoma cells or EBV-transformed B lymphocytes. The first 167 of the 497 amino acids of LMP2 retain full ability to associate with and act as a substrate for a tyrosine kinase. A 70-kDa phosphotyrosine cell protein associates with LMP2 in transfected cells or in EBV-transformed B lymphocytes and could be a mediator of the effects of LMP2.
Longnecker
R
R
Department of Microbiology and Molecular Genetics and Medicine, Harvard Medical School, Boston, Massachusetts.
Druker
B
B
Roberts
T M
TM
Kieff
E
E
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005455:Fluorescent Antibody Technique; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014763:Viral Matrix Proteins; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism*
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases