G. Alber et al., MOLECULAR MIMICRY OF THE ANTIGEN RECEPTOR SIGNALING MOTIF BY TRANSMEMBRANE PROTEINS OF THE EPSTEIN-BARR-VIRUS AND THE BOVINE LEUKEMIA-VIRUS, Current biology, 3(6), 1993, pp. 333-339
Background: Many transmembrane proteins of eukaryotic cells have only
a short cytoplasmic tail of 10 - 100 amino acids, which has no obvious
catalytic function. These tails are thought to be involved either in
signal transduction or in the association of transmembrane proteins wi
th the cytoskeleton. We have previously identified, in die cytoplasmic
tails of components of B and T lymphocyte antigen receptors, an amino
-acid motif that is required for signalling. The same motif is also fo
und in the cytoplasmic tails of two viral proteins: the latent membran
e protein, LMP2A, of Epstein-Barr virus and the envelope protein, gp30
, of bovine leukaemia virus. Interestingly, both viruses can activate
infected B lymphocytes to proliferate, as does signalling by B-cell re
ceptor. Results: In this study, we show that the cytoplasmic tails of
the two viral proteins, and the cytoplasmic tail of the B-cell recepto
r immunoglobulin-alpha chain, when linked to CD8 in chimeric transmemb
rane proteins, can transduce signals in B cells. Cross-linking of thes
e chimeric receptors activates B-cell protein tyrosine kinases and res
ults in calcium mobilization. Furthermore, these cytoplasmic sequences
are also protein tyrosine kinase substrates and may interact with cyt
osolic proteins carrying SH2 protein-protein interaction domains. Conc
lusion: Our findings suggest that viral transmembrane proteins can mim
ic the antigen-induced stimulation of the B-cell antigen receptor and
thus can influence the activation and/or survival of infected B lympho
cytes.