A NOVEL CYTOKINE-INDUCIBLE GENE CIS ENCODES AN SH2-CONTAINING PROTEIN THAT BINDS TO TYROSINE-PHOSPHORYLATED INTERLEUKIN-3 AND ERYTHROPOIETIN RECEPTORS

被引：625

作者：

YOSHIMURA, A

OHKUBO, T

KIGUCHI, T

JENKINS, NA

GILBERT, DJ

COPELAND, NG

HARA, T

MIYAJIMA, A

机构：

[1] DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304

[2] KAGOSHIMA UNIV,FAC MED,CANC RES INST,KAGOSHIMA 890,JAPAN

[3] KURUME UNIV,INST LIFE SCI,KURUME,FUKUOKA 830,JAPAN

[4] NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702

[5] UNIV TOKYO,INST MOLEC & CELLULAR BIOSCI,TOKYO 113,JAPAN

来源：

EMBO JOURNAL | 1995年 / 14卷 / 12期

关键词：

CYTOKINE; CYTOKINE RECEPTOR; IMMEDIATE-EARLY GENE; SH2; DOMAIN;

D O I：

10.1002/j.1460-2075.1995.tb07281.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2816 / 2826

页数：11

共 8 条

[1] Arai K., Lee F., Miyajima A., Miyatake S., Arai N., Yokota T., Cytokines: Coordinators of immune and inflammatory responses, Annu. Rev. Biochem., 59, pp. 783-836, (1990)
[2] Bazan J.F., Structural design and molecular evolution of a cytokine receptor superfamily, Proc. Nail Acad. Sci USA, 87, pp. 6934-6938, (1990)
[3] Copcland N.G., Jenkins N.A., Development and application of a molecular genetic linkage map of the mouse genome, Trends Genet., 7, pp. 113-118, (1991)
[4] Cutler R.L., Liu L., Damen J.F., Krystal G., Multiple cytokines induce the tyrosine phosphorylation of She and its association with Grb2 in hematopoietic cells, J. RM. Chem., 268, pp. 21463-21465, (1993)
[5] Darnell J.E.J., Kerr I.M., Stark G.R., Jak-STAT Pathways, (1994)
[6] Yoshimura A., Lodish H.F., In vitro phosphorylation of the erythropoictin receptor and an associated protein. pp130, Mol. Cell. Bioi., 12, pp. 706-715, (1992)
[7] Yoshimura A., D'Andrea A.D., Lodish H., Friend spleen focus-forming virus glycoprotein gp55 interacts with the erythropoietin receptor in the endoplasmic reticulum and affects receptor metabolism, Proc. Null Acad. Sci. USA., 87, pp. 4239-14143, (1990)
[8] Yoshimura A., Longmore G., Lodish H., Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity, Nature, 348, pp. 647-649, (1990)

← 1 →