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The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein‐Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events.
Author(s) -
Beaufils P.,
Choquet D.,
Mamoun R.Z.,
Malissen B.
Publication year - 1993
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1993.tb06205.x
Subject(s) - biology , cytoplasm , transmembrane domain , virus , microbiology and biotechnology , transmembrane protein , retrovirus , virology , gene , receptor , genetics
The cytoplasmic domains of the transducing subunits associated with B and T cell antigen receptors contain a common amino acid motif consisting of two precisely spaced Tyr‐X‐X‐Leu/Ile sequences (where X corresponds to a variable residue). Expression of a single copy of this motif suffices to initiate B or T cell activation. The bovine leukaemia virus (BLV) is a B cell lymphotropic retrovirus which causes a non‐neoplasic proliferation of B cells. The cytoplasmic domain of the BLV transmembrane envelope glycoprotein, gp30, possesses two overlapping copies of the Tyr‐X‐X‐Leu/Ile‐containing motif which could participate in the induction of B cell activation. Similarly, the N‐terminal cytoplasmic domain of the latent membrane protein 2A (LMP2A) of the Epstein‐Barr virus (EBV) contains a single copy of the Tyr‐X‐X‐Leu/Ile‐containing motif which could play a critical role in B cell transformation. To determine whether these two virus‐encoded cytoplasmic domains are endowed with signalling functions, we constructed chimeric proteins by replacing the cytoplasmic tail of CD8‐alpha with that of either BLV gp30 or EBV LMP2A. We show here that, once separately expressed in B or T cell lines, these chimeras are capable of triggering both calcium responses and cytokine production when cross‐linked with an antibody to CD8‐alpha. Furthermore, using site‐directed mutagenesis, we demonstrated unequivocally that this signalling function may be accounted for by the Tyr‐X‐X‐Leu/Ile motifs they contain.(ABSTRACT TRUNCATED AT 250 WORDS)