CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells

Ritsu Suzuki, Hiroshi Sakamoto, Hideo Yasukawa, Masaaki Masuhara, Toru Wakioka, Atsuo Sasaki, Kentaro Yuge, Setsuro Komiya, Akio Inoue, Akihiko Yoshimura

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Abstract

We have reported JAK-signaling modulators, CIS1 (cytokine-inducible SH2 protein-1), CIS3 and JAB (JAK2 binding protein), which are structurally related. In M1 myeloid leukemia cells, CIS3 was induced by neither interleukin 6 (IL6) nor interferon γ (IFNγ), while JAB was induced strongly by IFNγ and slightly by IL6 and leukemia inhibitory factor (ILF). Forced expression of CIS3 and JAB in M1 cells prevented IL6- or LIF-induced growth arrest and differentiation, even when their expression levels were comparable to endogenous ones in several cell lines such as HEL, UT-7, UFNγ-treated M1, and CTLL2 cells. Pretreatment of parental M1 cells with IFNγ but not IFNβ resulted in suppression of LIF-induced STAT3 activation and differentiation, further supporting that physiological level of JAB is sufficient to inhibit LIF-signaling. However, unlike JAB, CIS3 did not inhibit IFNγ-induced growth arrest, suggesting a difference in cytokine specificity between CIS3 and JAB. CIS3 inhibited STAT3 activation with slower kinetics than JAB and allowed rapid c-fos induction and partial FcγRI expression in response to IL6. In 293 cells, CIS3 as well as JAB bound to JAK2 tyrosine kinase domain (JH1), and inhibited its kinase activity, however, the effect of CIS3 on tyrosine kinase activity was weaker than that of JAB, indicating that CIS3 possesses lower affinity to JAK kinases than JAB. These findings suggest that CIS3 is a weaker inhibitor than JAB against JAK signaling, and JAB and CIS3 possess different regulatory roles in cytokine signaling.

Original languageEnglish
Pages (from-to)2271-2278
Number of pages8
JournalOncogene
Volume17
Issue number17
Publication statusPublished - 1998 Oct 29
Externally publishedYes

Fingerprint

Interleukin-6
Carrier Proteins
Leukemia
Interferons
Cytokines
Protein-Tyrosine Kinases
Janus Kinases
Leukemia Inhibitory Factor
Myeloid Leukemia
Myeloid Cells
Growth
Phosphotransferases
Cell Line

Keywords

  • Interleukin 6
  • JAK
  • Regulation
  • STAT
  • Tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Suzuki, R., Sakamoto, H., Yasukawa, H., Masuhara, M., Wakioka, T., Sasaki, A., ... Yoshimura, A. (1998). CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells. Oncogene, 17(17), 2271-2278.

CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells. / Suzuki, Ritsu; Sakamoto, Hiroshi; Yasukawa, Hideo; Masuhara, Masaaki; Wakioka, Toru; Sasaki, Atsuo; Yuge, Kentaro; Komiya, Setsuro; Inoue, Akio; Yoshimura, Akihiko.

In: Oncogene, Vol. 17, No. 17, 29.10.1998, p. 2271-2278.

Research output: Contribution to journalArticle

Suzuki, R, Sakamoto, H, Yasukawa, H, Masuhara, M, Wakioka, T, Sasaki, A, Yuge, K, Komiya, S, Inoue, A & Yoshimura, A 1998, 'CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells', Oncogene, vol. 17, no. 17, pp. 2271-2278.
Suzuki R, Sakamoto H, Yasukawa H, Masuhara M, Wakioka T, Sasaki A et al. CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells. Oncogene. 1998 Oct 29;17(17):2271-2278.
Suzuki, Ritsu ; Sakamoto, Hiroshi ; Yasukawa, Hideo ; Masuhara, Masaaki ; Wakioka, Toru ; Sasaki, Atsuo ; Yuge, Kentaro ; Komiya, Setsuro ; Inoue, Akio ; Yoshimura, Akihiko. / CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells. In: Oncogene. 1998 ; Vol. 17, No. 17. pp. 2271-2278.
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