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

Biochem Biophys Res Commun. 2004 Dec 17;325(3):758-68. doi: 10.1016/j.bbrc.2004.10.094.

Abstract

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.

MeSH terms

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

Substances

  • Carrier Proteins
  • Membrane Glycoproteins
  • NF-kappa B
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Transcription Factor AP-1
  • Proto-Oncogene Proteins pp60(c-src)