The role of the DAP12 signal in mouse myeloid differentiation.
DAP12 is a recently cloned, immunoreceptor tyrosine-based activation motif-bearing transmembrane adapter molecule that is associated with the NK-activating receptors. Previous reports showed that the DAP12 message could be detected not only in NK cells but also in granulocytes, monocytes, dendritic cells, and macrophages. In this study we found a significant level of DAP12 protein expression in macrophage-related cell lines and organs. Additionally, we observed increased expression of DAP12 after LPS-induced differentiation of M1 cells into macrophages. To examine the role of DAP12 in the myeloid cell lineage, we established M1 FLAG-DAP12 transfectants (FDAP-M1) and demonstrated the marked morphological changes in FDAP-M1 cells caused by signaling through DAP12. Cell surface phenotypic analysis showed up-regulation of macrophage markers CD11b, 2.4G2, and adhesion molecule B7-2. Additionally, after stimulation through DAP12, phosphorylated FLAG -DAP12 could be immunoprecipitated using anti-phosphotyrosine mAbs. Collectively, these findings indicate that direct DAP12 signaling has an important role in macrophage differentiation.
Aoki
N
N
Department of Pathology, Asahikawa Medical College, Japan. aoq@asahikawa-med.ac.jp
Kimura
S
S
Takiyama
Y
Y
Atsuta
Y
Y
Abe
A
A
Sato
K
K
Katagiri
M
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D007941:Leukemia P388; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D009842:Oligopeptides / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D009928:Organ Specificity / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009842:Oligopeptides; D010455:Peptides; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C110546:TYROBP protein, human; C085706:FLAG peptide