CD48, a ligand of CD244, possesses no ITSM in its cytoplasmic tail [1] and [15]. caauCD2f-1 and caauCD2f-2 have two and three ITSMs, respectively, whereas no ITSM motif is found in the cytoplasmic tails of caauCD2f-3 and caauCD2f-4. Therefore, comparison of the primary structures and the presence of ITSMs in caauCD2f and the mammalian CD2 family indicates that caauCD2f-1 and caauCD2f-2 may have functional similarity to CD244 and/or CD319 and caauCD2f-3 and caauCD2f-3–4 may correspond to CD48. The

murine CD244 gene encodes two different isoforms (2B4 short and 2B4 long) that arise by alternative splicing, resulting in a different number of ITSMs in their cytoplasmic tails. The murine 2B4 isoforms have been shown to have opposing functions as the long form has an inhibitory function and the

short form has an activating function [5], [21] and [29]. However, www.selleckchem.com/products/LBH-589.html Everolimus it seems unlikely that the caauCD2f isoforms have arisen from alternative splicing because the sequences of their extracellular domains are not identical. As the caauCD2f isoforms possess different number of ITSMs, they may exhibit different functions depending on the number of ITSMs similar to murine CD244. Taken together with the results relating to the differential expression of the caauCD2f isoforms, each caauCD2f can be considered as a distinct receptor that has various functions. In mammals, CD2fs are displayed on various types of leukocytes, such as T-cells, B-cells, NK-cells, macrophages, and DC cells. caauCD2f-1 and caauCD2f-2, which posses ITSM motifs,

are dominantly expressed by CTL and other lymphocytes except for Th cells. In contrast, it is suggested that caauCD2f-4, which has no ITSM, is expressed by Th cells, Reverse transcriptase while it is also expressed on other cells except for Ig-positive cells. Also, the expression pattern of caauCD2fs is different between adherent and non-adherent cells. These findings indicate that each caauCD2f has acquired distinct functions after divergence from their ancestral Ig-like receptors. Further functional studies at the cellular level employing this clonal fish and its cell markers would contribute to furthering our understanding of the functional differentiation of the four caauCD2fs. The genes of the human CD2f were mapped into two clusters [8] and [22]. CD2 and CD58 are on the short arm of chromosome 1, separated from the other members, which are clustered together on the long arm of chromosome 1. Genomic analysis of zebrafish CD2f genes indicates that the two clusters of the CD2f genes are present on different chromosomes (chromosome 1 or 2). On the other hand, zebrafish CD2-like genes are located on a different locus to the CD2f genes. Three CD2-like genes formed a small cluster on this locus, suggesting that these zebrafish CD2 genes were generated through tandem gene duplications.