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Cloning and Functional Analysis of New Members of STAT Induced STAT Inhibitor (SSI) Family: SSI-2 and SSI-3

https://doi.org/10.1006/bbrc.1997.7080Get rights and content

Abstract

Upon the corresponding ligand's stimulation, the cytokine receptors activate several signal pathways: JAK-STAT pathway, Ras-MAP kinase pathway and so on. Recently, we demonstrated that one of the STAT3 (signal transducer and activator of transcription-3) target genes could suppress the function of STAT3 and designated as SSI-1(STAT induced STAT inhibitor-1). SSI-1 is thought to play a critical role in negative feedback control of JAK-STAT signaling pathway. In the present study, we identified two novel human genes which products have homologous region in their SH2 domain and its COOH-terminal region to mouse SSI-1. Northern blotting analysis and functional studies demonstrated that SSI-2 and SSI-3 mRNA were also induced by cytokine stimulation and their forced expression in mouse myeloid leukemia cell, M1, suppressed the apoptotic effect of LIF, like SSI-1. We also demonstrated the structure of human SSI-1.

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Cited by (144)

  • JAK1-mediated Sirt1 phosphorylation functions as a negative feedback of the JAK1-STAT3 pathway

    2018, Journal of Biological Chemistry
    Citation Excerpt :

    Our studies suggest JAK1-mediated Sirt1 phosphorylation as a possible common molecular feedback for the JAK1-STAT3 signaling pathways. In addition to this Sirt1-mediated deacetylation event, previous studies have defined that the posttranslational modification, either by ubiquitin catalyzed by the SOCS family E3 ubiquitin ligase (21, 29) or by the small ubiquitin-like modifier (SUMO) catalyzed by PIAS family proteins, plays critical roles in negatively regulating the JAK-STAT pathways (30). Therefore, the cytokine-induced JAK1-STAT3 activation appears to be controlled by multiple negative regulations.

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IL, interleukinJAK, Janus kinase; STAT, signal transducer and activator of transcription; SSI, STAT induced STAT inhibitor; CIS, cytokine inducible SH2 protein; Epo, erythropoietin; GM-CSF, granulocyte macrophage colony stimulating factor; PBL, peripheral blood lymphocyte;

1

These authors contributed equally.

2

Corresponding author. Fax: 81 (06) 879-3839.

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