SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration

Sho Tokumaru, Koji Sayama, Kenshi Yamasaki, Yuji Shirakata, Yasushi Hanakawa, Yoko Yahata, Xiuju Dai, Mikiko Tohyama, Lujun Yang, Akihiko Yoshimura, Koji Hashimoto

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23 Citations (Scopus)

Abstract

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes. Because HGF has strong effects on the motility of keratinocytes and is produced by fibroblasts, HGF is thought to regulate keratinocyte migration during wound healing. However, the intracellular signaling mechanism of HGF-induced keratinocyte migration is poorly understood. In this report, we clarify the roles of STAT3 and SOCS/CIS family in HGF-induced keratinocyte migration. HGF activated STAT3 and strongly induced keratinocyte migration. Transfection with the dominant-negative mutant of STAT3 almost completely abolished HGF-induced keratinocyte migration and STAT3 phosphorylation. Next, we studied the mechanisms that regulate STAT3 phosphorylation. HGF enhanced the expression of SOCS3/CIS3 by sixfold within 1 h, but had minimum effect on SOCS1/JAB expression. Transfection with SOCS3/CIS3 almost completely abolished HGF-induced STAT3 phosphorylation and keratinocyte migration, indicating that SOCS3/CIS3 acts as a negative regulator of HGF-induced keratinocyte migration. In conclusion, SOCS3/CIS3 regulates HGF-induced keratinocyte migration by inhibiting STAT3 phosphorylation.

Original languageEnglish
Pages (from-to)100-105
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume327
Issue number1
DOIs
Publication statusPublished - 2005 Feb 4

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Keywords

  • Adenovirus vector
  • HGF
  • Keratinocytes
  • Migration
  • SOCS1/JAB
  • SOCS3/CIS3
  • STAT1
  • STAT3
  • Wound healing

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tokumaru, S., Sayama, K., Yamasaki, K., Shirakata, Y., Hanakawa, Y., Yahata, Y., Dai, X., Tohyama, M., Yang, L., Yoshimura, A., & Hashimoto, K. (2005). SOCS3/CIS3 negative regulation of STAT3 in HGF-induced keratinocyte migration. Biochemical and Biophysical Research Communications, 327(1), 100-105. https://doi.org/10.1016/j.bbrc.2004.11.145