Ly49Q, a Member of the Ly49 Family That Is Selectively Expressed on Myeloid Lineage Cells and Involved in Regulation of Cytoskeletal Architecture

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 4; pp. 1016 - 1021
• Main Authors: Toyama-Sorimachi, Noriko, Tsujimura, Yusuke, Maruya, Mikako, Onoda, Atsuko, Kubota, Toshiyuki, Koyasu, Shigeo, Inaba, Kayo, Karasuyama, Hajime
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27-01-2004; National Acad Sciences
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antigens, Ly - immunology; Antigens, Ly - metabolism; Base Sequence; Biological Sciences; Bone marrow; Bone marrow cells; Bone Marrow Cells - metabolism; Cell Lineage; Cell lines; Cloning, Molecular; Complementary DNA; Cytoskeleton; Cytoskeleton - metabolism; DNA Primers; DNA, Complementary; Family members; Flow Cytometry; Gene Expression Regulation; Genes; Immunology; Lectins, C-Type; Ly49q gene; Macrophages; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Molecules; Natural killer cells; Natural killer T cells; NK Cell Lectin-Like Receptor Subfamily A; Phosphorylation; Polymerase Chain Reaction; Proteins; Receptors; Receptors, NK Cell Lectin-Like; SHP-1 protein; SHP-2 protein; Tyrosine - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0305400101

Here, we identified and characterized a Ly49 family member, designated as Ly49Q. The Ly49q gene encodes a 273-aa protein with an immunoreceptor tyrosine-based inhibitory motif (ITIM) at the N terminus of its cytoplasmic domain. We show that the ITIM of Ly49Q can recruit SHP-2 and SHP-1 in a tyrosine phosphorylation-dependent manner. In contrast to other known members of the Ly49 family, Ly49Q was found not to be expressed on NK1.1+cells, but instead was detectable on virtually all Gr-1+cells, such as myeloid precursors in bone marrow. Monocytes/macrophages also expressed low levels of Ly49Q, and the expression was enhanced by the treatment of cells with IFN-γ. Treatment of activated macrophages with anti-Ly49Q mAb induced rapid formation of polarized actin structures, showing filopodia-like structure on one side and lamellipodial-like structure on the other side. A panel of proteins became tyrosine-phosphorylated in myeloid cells when treated with the mAb. Induction of the phosphorylation depends on the ITIM of Ly49Q. Thus, Ly49Q has unique features different from other known Ly49 family members and appears to be involved in regulation of cytoskeletal architecture of macrophages through ITIM-mediated signaling.