Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture.
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-gamma. 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.
Toyama-Sorimachi
Noriko
N
Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. n-sori.mbch@tmd.ac.jp
Tsujimura
Yusuke
Y
Maruya
Mikako
M
Onoda
Atsuko
A
Kubota
Toshiyuki
T
Koyasu
Shigeo
S
Inaba
Kayo
K
Karasuyama
Hajime
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism*; D019070:Cell Lineage; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism*; D017931:DNA Primers; D018076:DNA, Complementary; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D037181:Lectins, C-Type; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055650:NK Cell Lectin-Like Receptor Subfamily A; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D055630:Receptors, NK Cell Lectin-Like; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D017931:DNA Primers; D018076:DNA, Complementary; C527089:Klra17 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like; D014443:Tyrosine