CMRF-35-like molecule-5 constitutes novel paired receptors, with CMRF-35-like molecule-1, to transduce activation signal upon association with FcRγ

The murine CMRF-35-like molecule (CLM) family belongs to the Ig superfamily, and consists of nine mapped genes. Here we report that CLM-5 and CLM-1 constitute novel paired Ig-like receptors (PIRs). CLM-1 and CLM-5 genes are encoded in close vicinity on chromosome 11. CLM-1 has been reported to possess immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic region and to inhibit the differentiation of osteoclast. CLM-5 has an Ig domain that is highly homologous with that of CLM-1 in its extracellular domain, and possesses a negatively charged residue in its transmembrane domain. CLM-5, like CLM-1, is expressed in myeloid cells, such as dendritic cells, macrophages and granulocytes. We also show that CLM-5 interacts with FcR gamma to be expressed on the plasma membrane and that the cross-linking of CLM-5 leads to tyrosine phosphorylation of proteins, including FcR gamma, in the monocyte/macrophage cell line. Taken together, these characteristics suggest that CLM-1 and CLM-5 constitute novel PIRs and that CLM-5 may transduce activation signals as the activating receptor in myeloid cells.