Induction of mouse c-src in RAW264 cells is dependent on AP-1 and NF-kappaB and important for progression to multinucleated cell formation.
C-src is known to play an essential role in osteoclastogenesis. We studied the regulatory mechanism as well as the significance of c-src induction in RANKL-induced differentiation of mouse monocytic RAW264 cells to TRAP-positive-multinucleated cells. We determined the genomic organization of the 5'-terminal region of mouse c-src. Mutational and biochemical analyses in the region 0.9 kb upstream of the transcription start site revealed that c-Fos and JNK pathways, in addition to NF-kappaB, participate in c-src induction in response to RANKL. On the other hand, when the expression of c-src was suppressed by introducing antisense src, the number of multinucleated cells formed was significantly reduced. Together, these findings show that the expression of c-src is under the control of AP-1 and NF-kappaB in the differentiation of RAW264 cells and that c-src plays an essential role at the stage of progression to multinucleated cell formation.
Kumagai
Naoko
N
Graduate School of Biological Sciences, NAIST, Ikoma, Nara 630-0101, Japan.
Ohno
Keita
K
Tameshige
Ryusuke
R
Hoshijima
Mitsuhiro
M
Yogo
Keiichiro
K
Ishida
Norihiro
N
Takeya
Tatsuo
T
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D015726:Giant Cells / Q000166:cytology* / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D018808:Transcription Factor AP-1; D016392:Proto-Oncogene Proteins pp60(c-src)