Induction of mouse c-src in RAW264 cells is dependent on AP-1 and NF-kappaB and important for progression to multinucleated cell formation

Naoko Kumagai, Keita Ohno, Ryusuke Tameshige, Mitsuhiro Hoshijima, Keiichiro Yogo, Norihiro Ishida, Tatsuo Takeya

Research output: Contribution to journalArticle

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)758-68
Number of pages11
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - Dec 17 2004



  • Animals
  • Carrier Proteins
  • Cell Differentiation
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • Giant Cells
  • Macrophages
  • Membrane Glycoproteins
  • Mice
  • NF-kappa B
  • Proto-Oncogene Proteins pp60(c-src)
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Transcription Factor AP-1
  • Journal Article

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