Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad

Takahiro Nakahara, Kazuhiro Tominaga, Takeyoshi Koseki, Matsuo Yamamoto, Kenji Yamato, Jinichi Fukuda, Tatsuji Nishihara

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Bone morphogenetic proteins, including growth/differentiation factor-5 (GDF-5), are multifunctional cytokines. Recent studies of intracellular signal transduction mechanisms for the transforming growth factor-β superfamily have focused on Smad proteins. However, scant attention has been given to the mechanism by which GDF-5 exerts its negative growth effect on immunological competent cells. In the present study, we demonstrated that GDF-5 induced cell cycle arrest in the G1 phase before the appearance of apoptosis in mouse B cell hybridoma HS-72 cells, while the ectopic expression of Smad6 and Smad7 in HS-72 cells suppressed the GDF-5-induced G1 cell cycle arrest by abolishing the expression of p21CIP-1/WAF-1 and hypophosphorylation of retinoblastoma protein. Moreover, we found that Smad6 and Smad7 suppressed GDF-5-induced apoptosis in HS-72 cells. These findings indicated that Smad6 and Smad7 exhibit inhibitory effects toward GDF-5-mediated signaling in B lineage cells.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalCellular Signalling
Volume15
Issue number2
DOIs
Publication statusPublished - 2003 Feb 1
Externally publishedYes

Keywords

  • Apoptosis
  • B cells
  • BMP
  • GDF-5
  • Growth arrest
  • Smad
  • TGF-β super family

ASJC Scopus subject areas

  • Cell Biology

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