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)

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.

Original languageEnglish
Pages (from-to)758-68
Number of pages11
JournalBiochemical and Biophysical Research Communications
Volume325
Issue number3
DOIs
Publication statusPublished - Dec 17 2004

Fingerprint

NF-kappa B
Transcription Factor AP-1
Transcription Initiation Site
MAP Kinase Signaling System
Osteogenesis
Cell Differentiation
Cell Count

Keywords

  • 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

Cite this

Induction of mouse c-src in RAW264 cells is dependent on AP-1 and NF-kappaB and important for progression to multinucleated cell formation. / Kumagai, Naoko; Ohno, Keita; Tameshige, Ryusuke; Hoshijima, Mitsuhiro; Yogo, Keiichiro; Ishida, Norihiro; Takeya, Tatsuo.

In: Biochemical and Biophysical Research Communications, Vol. 325, No. 3, 17.12.2004, p. 758-68.

Research output: Contribution to journalArticle

Kumagai, Naoko ; Ohno, Keita ; Tameshige, Ryusuke ; Hoshijima, Mitsuhiro ; Yogo, Keiichiro ; Ishida, Norihiro ; Takeya, Tatsuo. / Induction of mouse c-src in RAW264 cells is dependent on AP-1 and NF-kappaB and important for progression to multinucleated cell formation. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 325, No. 3. pp. 758-68.
@article{499e1152bdf340c38e59ca65ab6858a3,
title = "Induction of mouse c-src in RAW264 cells is dependent on AP-1 and NF-kappaB and important for progression to multinucleated cell formation",
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.",
keywords = "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",
author = "Naoko Kumagai and Keita Ohno and Ryusuke Tameshige and Mitsuhiro Hoshijima and Keiichiro Yogo and Norihiro Ishida and Tatsuo Takeya",
year = "2004",
month = "12",
day = "17",
doi = "10.1016/j.bbrc.2004.10.094",
language = "English",
volume = "325",
pages = "758--68",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Induction of mouse c-src in RAW264 cells is dependent on AP-1 and NF-kappaB and important for progression to multinucleated cell formation

AU - Kumagai, Naoko

AU - Ohno, Keita

AU - Tameshige, Ryusuke

AU - Hoshijima, Mitsuhiro

AU - Yogo, Keiichiro

AU - Ishida, Norihiro

AU - Takeya, Tatsuo

PY - 2004/12/17

Y1 - 2004/12/17

N2 - 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.

AB - 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.

KW - Animals

KW - Carrier Proteins

KW - Cell Differentiation

KW - Cell Proliferation

KW - Dose-Response Relationship, Drug

KW - Gene Expression Regulation

KW - Giant Cells

KW - Macrophages

KW - Membrane Glycoproteins

KW - Mice

KW - NF-kappa B

KW - Proto-Oncogene Proteins pp60(c-src)

KW - RANK Ligand

KW - Receptor Activator of Nuclear Factor-kappa B

KW - Transcription Factor AP-1

KW - Journal Article

U2 - 10.1016/j.bbrc.2004.10.094

DO - 10.1016/j.bbrc.2004.10.094

M3 - Article

C2 - 15541355

VL - 325

SP - 758

EP - 768

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -