TY - JOUR
T1 - Essential role of DAP12 signaling in macrophage programming into a fusion-competent state
AU - Helming, Laura
AU - Tomasello, Elena
AU - Kyriakides, Themis R.
AU - Martinez, Fernando O.
AU - Takai, Toshiyuki
AU - Gordon, Siamon
AU - Vivier, Eric
PY - 2008/10/28
Y1 - 2008/10/28
N2 - Multinucleated giant cells, formed by fusion of macrophages, are a hallmark of granulomatous inflammation. With a genetic approach, we show that signaling through the adaptor protein DAP12 (DNAX activating protein of 12 kD), its associated receptor triggering receptor expressed by myeloid cells 2 (TREM-2), and the downstream protein tyrosine kinase Syk is required for the cytokineinduced formation of giant cells and that overexpression of DAP12 potentiates macrophage fusion. We also present evidence that DAP12 is a general macrophage fusion regulator and is involved in modulating the expression of several macrophage-associated genes, including those encoding known mediators of macrophage fusion, such as DC-STAMP and Cadherin 1. Thus, DAP12 is involved in programming of macrophages through the regulation of gene and protein expression to induce a fusion-competent state.
AB - Multinucleated giant cells, formed by fusion of macrophages, are a hallmark of granulomatous inflammation. With a genetic approach, we show that signaling through the adaptor protein DAP12 (DNAX activating protein of 12 kD), its associated receptor triggering receptor expressed by myeloid cells 2 (TREM-2), and the downstream protein tyrosine kinase Syk is required for the cytokineinduced formation of giant cells and that overexpression of DAP12 potentiates macrophage fusion. We also present evidence that DAP12 is a general macrophage fusion regulator and is involved in modulating the expression of several macrophage-associated genes, including those encoding known mediators of macrophage fusion, such as DC-STAMP and Cadherin 1. Thus, DAP12 is involved in programming of macrophages through the regulation of gene and protein expression to induce a fusion-competent state.
UR - http://www.scopus.com/inward/record.url?scp=58149195670&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149195670&partnerID=8YFLogxK
U2 - 10.1126/scisignal.1159665
DO - 10.1126/scisignal.1159665
M3 - Article
C2 - 18957693
AN - SCOPUS:58149195670
VL - 1
JO - Science's STKE : signal transduction knowledge environment
JF - Science's STKE : signal transduction knowledge environment
SN - 1937-9145
IS - 43
M1 - ra11
ER -