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.
MeSH Terms
Amino Acid Sequence
Animals
Carrier Proteins/biosynthesis,chemistry,metabolism
Cell Division/drug effects
Cell Line
Cloning, Molecular
Cytokines/pharmacology
DNA-Binding Proteins
Female
Growth Inhibitors/pharmacology
Humans
Interleukin-6
Intracellular Signaling Peptides and Proteins
Leukemia Inhibitory Factor
Lymphokines/pharmacology
Male
Mice
Molecular Sequence Data
Organ Specificity
Proteins
RNA, Messenger/biosynthesis
Recombinant Proteins/biosynthesis,chemistry,metabolism
Repressor Proteins
Sequence Alignment
Sequence Homology, Amino Acid
Signal Transduction
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Trans-Activators
Transcription Factors
Transcription, Genetic/drug effects
Transfection
Chemicals
Carrier Proteins
Cytokines
DNA-Binding Proteins
Growth Inhibitors
Interleukin-6
Intracellular Signaling Peptides and Proteins
LIF protein, human
Leukemia Inhibitory Factor
Lif protein, mouse
Lymphokines
Proteins
RNA, Messenger
Recombinant Proteins
Repressor Proteins
SOCS1 protein, human
SOCS2 protein, human
SOCS3 protein, human
Socs1 protein, mouse
Socs2 protein, mouse
Socs3 protein, mouse
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Trans-Activators
Transcription Factors
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Minamoto S
Department of Medicine III, Osaka University Medical School, Suita, Japan.
Ikegame K
Ueno K
Narazaki M
Naka T
Yamamoto H
Matsumoto T
Saito H
Hosoe S
Kishimoto T