WW- and SH3-domain interactions with Epstein-Barr virus LMP2A.
Epstein-Barr virus (EBV) is a human herpesvirus which establishes a lifelong latent infection in B lymphocytes. Latent membrane protein 2A (LMP2A) is expressed in both humans with EBV latent infection and EBV immortalized cell lines grown in culture. Previous studies have shown that the amino terminal domain of LMP2A, which contains eight tyrosines, associates with a variety of cellular proteins via SH2-phosphotyrosine interactions. Also contained within the LMP2A amino terminal domain are five proline-rich regions, three of which possess the PxxP core consensus sequence required for interacting with SH3 domains and two of which possess the PPxY core consensus sequence (PY motif) required for interacting with class I type WW domains. In the current study, the ability of LMP2A to interact with either modular SH3 or WW domains was investigated. The results of these studies indicate that the two LMP2A PY motifs interact strongly with representative class I WW domains, but not with representative class II WW domains. In contrast, no interactions were detected between LMP2A and any of the five different SH3 domains tested. These data demonstrate that a subset of the conserved proline-rich motifs within the amino terminus of LMP2A can potentially mediate interactions with cellular proteins and may play a role in EBV-mediated latency and/or transformation.
Longnecker
R
R
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois, 60611, USA. r-longnecker@nwu.edu
Merchant
M
M
Brown
M E
ME
Fruehling
S
S
Bickford
J O
JO
Ikeda
M
M
Harty
R N
RN
D000595:Amino Acid Sequence; D001665:Binding Sites; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; D005982:Glutathione Transferase; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases