Document Detail

A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors.
MedLine Citation:
PMID:  7796808     Owner:  NLM     Status:  MEDLINE    
Cytokines manifest their function through alteration of gene expression. However, target genes for signals from cytokine receptors are largely unknown. We therefore searched for immediate-early cytokine-responsive genes and isolated a novel gene, CIS (cytokine inducible SH2-containing protein) which is induced in hematopoietic cells by a subset of cytokines including interleukin 2 (IL2), IL3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), but not by stem cell factor, granulocyte colony-stimulating factor and IL6. The CIS message encodes a polypeptide of 257 amino acids that contains an SH2 domain of 96 amino acids in the middle. To clarify the function of CIS in cytokine signal transduction, we expressed CIS in IL3-dependent hematopoietic cell lines under the control of a steroid-inducible promoter. The CIS product stably associated with the tyrosine-phosphorylated beta chain of the IL3 receptor as well as the tyrosine-phosphorylated EPO receptor. Forced expression of CIS by steroid reduced the growth rate of these transformants, suggesting a negative role of CIS in signal transduction. CIS induction requires the membrane-proximal region of the cytoplasmic domain of the EPO receptor as well as that of the common beta chain of the IL3, IL5 and GM-CSF receptor, whereas CIS binds to the receptor that is tyrosine phosphorylated by cytokine stimulation. Thus CIS appears to be a unique regulatory molecule for cytokine signal transduction.
A Yoshimura; T Ohkubo; T Kiguchi; N A Jenkins; D J Gilbert; N G Copeland; T Hara; A Miyajima
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The EMBO journal     Volume:  14     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-08-03     Completed Date:  1995-08-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2816-26     Citation Subset:  IM    
Cancer Research Institute, Faculty of Medicine, Kagoshima University, Japan.
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MeSH Terms
Amino Acid Sequence
Base Sequence
Cell Line
Chromosome Mapping
Cloning, Molecular / methods
Gene Expression Regulation / drug effects*
Gene Library
Genes, Immediate-Early / genetics*
Growth Substances / pharmacology*
Hematopoietic Stem Cells
Immediate-Early Proteins / chemistry,  genetics*,  metabolism
Molecular Sequence Data
Organ Specificity
RNA, Messenger / analysis
Receptors, Erythropoietin / metabolism
Receptors, Interleukin-3 / metabolism
Recombinant Fusion Proteins / biosynthesis,  metabolism
Sequence Analysis, DNA
Signal Transduction / drug effects,  genetics
Suppressor of Cytokine Signaling Proteins
Tyrosine / metabolism
Grant Support
Reg. No./Substance:
0/Growth Substances; 0/Immediate-Early Proteins; 0/RNA, Messenger; 0/Receptors, Erythropoietin; 0/Receptors, Interleukin-3; 0/Recombinant Fusion Proteins; 0/Suppressor of Cytokine Signaling Proteins; 0/cytokine inducible SH2-containing protein; 55520-40-6/Tyrosine

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