DAP12 ITAM motif regulates differentiation and apoptosis in M1 leukemia cells.
DAP12 is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing transmembrane adapter molecule that is associated with the NK-activating receptors. DAP12 is expressed not only in NK cells, but also in myeloid cells. Previously, we reported that DAP12 was likely to be involved in monocyte differentiation to macrophage. In this study, we established the mutant DAP12-M1 transfectants (Y76F-M1) that have mutation at their ITAM motifs. We observed that Y76F-M1 cells could not differentiate to macrophages by stimulation via DAP12, whereas wild type DAP12 transfectants (FDAP-M1) could. Furthermore, we demonstrated that the apoptosis signal mediated by LPS was inhibited in Y76F-M1 cells, but was augmented in FDAP-M1 cells. In contrast to the LPS-mediated apoptosis, the combination of LPS and DAP12 stimulation showed good cell viability in FDAP-M1 cells. Collectively our studies demonstrated that DAP12 has a critical role for macrophage differentiation and LPS induced apoptosis in M1 leukemia cells.
Aoki
Naoko
N
Department of Pathology, Asahikawa Medical College, Asahikawa, Japan. aoq@asahikawa-med.ac.jp
Kimura
Shoji
S
Oikawa
Kensuke
K
Nochi
Hitoshi
H
Atsuta
Yoshiaki
Y
Kobayashi
Hiroya
H
Sato
Keisuke
K
Katagiri
Makoto
M
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012334:RNA, Neoplasm; D011971:Receptors, Immunologic; C110546:TYROBP protein, human