The box1 domain of the erythropoietin receptor specifies Janus kinase 2 activation and functions mitogenically within an interleukin 2 beta-receptor chimera

被引:53
作者
Jiang, N
He, TC
Miyajima, A
Wojchowski, DM
机构
[1] PENN STATE UNIV,GRAD PROGRAM PATHOBIOL & VET SCI,UNIVERSITY PK,PA 16802
[2] PENN STATE UNIV,GRAD PROGRAM GENET,UNIVERSITY PK,PA 16802
[3] PENN STATE UNIV,GRAD PROGRAM BIOCHEM & MOLEC BIOL,UNIVERSITY PK,PA 16802
[4] PENN STATE UNIV,CTR GENE REGULAT,UNIVERSITY PK,PA 16802
[5] UNIV TOKYO,INST MOLEC & CELLULAR BIOSCI,TOKYO,JAPAN
关键词
D O I
10.1074/jbc.271.28.16472
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
Several distinct classes of cytokine receptors engage Jak kinases as primary effecters. Among type 1 receptors, Janus activated kinase (Jak) recruitment is mediated by membrane-proximal cytoplasmic domains, which typically contain conserved box motifs. In the erythropoietin receptor (Epo-R), two such motifs (box1 and box2) have been suggested to be essential for the activation of Jak2 and mitogenesis, Presently, an Epo-R chimera containing the extracellular and box1 domains of the Epo-R (Jak2-associated receptor) and the box2 and carboxyl-terminal domains of the interleukin 2 beta-receptor (IL2 beta-R; a Jak1-associated subunit) is shown to activate Jak2. Interestingly, Jak2 also was activated in FDC-beta 1 cells by a control Epo-R chimera containing the complete IL2 beta-R cytoplasmic domain, and mitogenesis was supported by each of these above chimeras. By comparison, in BaF3 cells expressing IL2 receptor alpha and gamma subunits, an ectopically expressed IL2 beta-R chimera containing the box1 domain of the Epo-R, activated Jak2 and Jak3 and was as mitogenically active as the wild-type IL2 beta-R (Jak1 and Jak3 activation). Thus, the box1 domain of the Epo-R specifies Jak2 activation and functions efficiently within a heterologous IL2 receptor complex that normally activates Jak1 and Jak8.
引用
收藏
页码:16472 / 16476
页数:5
相关论文
共 39 条
[1]   ERYTHROPOIETIN AND INTERLEUKIN-2 ACTIVATE DISTINCT JAK KINASE FAMILY MEMBERS [J].
BARBER, DL ;
DANDREA, AD .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (10) :6506-6514
[3]   TYROSINE KINASE ACTIVATION THROUGH THE EXTRACELLULAR DOMAINS OF CYTOKINE RECEPTORS [J].
CHIBA, T ;
NAGATA, Y ;
MACHIDE, M ;
KISHI, A ;
AMANUMA, H ;
SUGIYAMA, M ;
TODOKORO, K .
NATURE, 1993, 362 (6421) :646-648
[4]   FUNCTIONALLY ESSENTIAL CYTOPLASMIC DOMAIN OF THE ERYTHROPOIETIN RECEPTOR [J].
CHIBA, T ;
KISHI, A ;
SUGIYAMA, M ;
AMANUMA, H ;
MACHIDE, M ;
NAGATA, Y ;
TODOKORO, K .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 186 (03) :1236-1241
[5]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[6]  
COLOSI P, 1993, J BIOL CHEM, V268, P12617
[7]   JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].
DARNELL, JE ;
KERR, IM ;
STARK, GR .
SCIENCE, 1994, 264 (5164) :1415-1421
[8]   GROWTH OF FACTOR-DEPENDENT HEMATOPOIETIC PRECURSOR CELL-LINES [J].
DEXTER, TM ;
GARLAND, J ;
SCOTT, D ;
SCOLNICK, E ;
METCALF, D .
JOURNAL OF EXPERIMENTAL MEDICINE, 1980, 152 (04) :1036-1047
[9]   A LIMITED CYTOPLASMIC REGION OF THE PROLACTIN RECEPTOR CRITICAL FOR SIGNAL-TRANSDUCTION [J].
EDERY, M ;
LEVIMEYRUEIS, C ;
PALY, J ;
KELLY, PA ;
DJIANE, J .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1994, 102 (1-2) :39-44
[10]   FUNCTIONAL DOMAINS OF THE GRANULOCYTE COLONY-STIMULATING FACTOR RECEPTOR [J].
FUKUNAGA, R ;
ISHIZAKAIKEDA, E ;
PAN, CX ;
SETO, Y ;
NAGATA, S .
EMBO JOURNAL, 1991, 10 (10) :2855-2865