The JAK-inhibitor, JAB/SOCS-1 selectively inhibits, cytokine-induced, but not v-Src induced JAK-STAT activation

Takashi Iwamoto, Takeshi Senga, Yuko Naito, Satoru Matsuda, Yozo Miyake, Akihiko Yoshimura, Michinari Hamaguchi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Recently, constitutive activation of JAK kinases (JAKs) and/or signal transducers and activators of transcription (STATs) has been reported in growing numbers of human cancer cells as well as oncogene-transformed cells. JAB/SOCS-1 has been shown to be an intrinsic JAK tyrosine kinase inhibitor and to suppress the cytokine-dependent JAK-STAT pathway. In this report, we investigated the effect of ectopic expression of JAB on v-Src-induced JAK-STAT activation. Forced expression of JAB in v-Src-transformed NIH3T3 cells neither suppressed phosphorylation of STAT3 and JAK1/JAK2 nor blocked STAT3-reporter gene activation. Colony forming assay also showed that JAB did not suppress v-Src-lnduced transformation of NIH3T3 cells, while dominant negative STAT3 suppressed it. In contrast, JAB could downregulate pbospborylation of STAT1 and STAT3 induced by interferon gamma (IFN(γ)) and interleukin-6 (IL-6) plus soluble IL6 receptor (sIL-6R), respectively. Furthermore, in vitro kinase assay indicated that JAB suppressed byperactivation of JAK1/JAK2 and JAK1 induced by INF(γ) and IL-6 plus sIL-6R respectively, but not v-Src-induced basal JAKI/JAK2 activity. Nevertheless, both JAK1/JAK2 activated by v-Src and that activated by IL-6 plus slL-6R could similarly bind JAB. These results clearly demonstrate that JAB distinguishes cytokine-induced JAK-STAT signaling from v-Src-induced one and can not suppress the transformation with v-Src.

Original languageEnglish
Pages (from-to)4795-4801
Number of pages7
JournalOncogene
Volume19
Issue number41
Publication statusPublished - 2000 Sep 28
Externally publishedYes

    Fingerprint

Keywords

  • Cytokine
  • JAB
  • JAK
  • Src
  • STAT

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Iwamoto, T., Senga, T., Naito, Y., Matsuda, S., Miyake, Y., Yoshimura, A., & Hamaguchi, M. (2000). The JAK-inhibitor, JAB/SOCS-1 selectively inhibits, cytokine-induced, but not v-Src induced JAK-STAT activation. Oncogene, 19(41), 4795-4801.