Receptors for interleukin (IL)-10 and IL-6-type cytokines use similar signaling mechanisms for inducing transcription through IL-6 response elements

被引:86
作者
Lai, CF
Ripperger, J
Morella, KK
Jurlander, J
Hawley, TS
Carson, WE
Kordula, T
Caliguri, MA
Hawley, RG
Fey, GH
Baumann, H
机构
[1] ROSWELL PK CANC INST,DEPT MOLEC & CELLULAR BIOL,BUFFALO,NY 14263
[2] ROSWELL PK CANC INST,DEPT MED & SURG,BUFFALO,NY 14263
[3] UNIV ERLANGEN NURNBERG,D-91068 ERLANGEN,GERMANY
[4] TORONTO HOSP,ONCOL RES LABS,TORONTO,ON M5G 2M1,CANADA
[5] UNIV GEORGIA,DEPT BIOCHEM,ATHENS,GA 30602
关键词
D O I
10.1074/jbc.271.24.13968
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
The cytoplasmic domain of the receptor for interleukin 10 (IL-10R) contains two box 3 sequence motifs that have been identified in the signal-transducing receptor subunits for IL-6-type cytokines and noted to be required for activating STAT3 and inducing transcription through IL-B-responsive elements, To determine whether the IL-10R has signaling functions similar to IL-6R in cells normally expressing these receptors, leukocytes of the B-, T-, and NK cell lineages were treated with either cytokine, Both cytokines activated factors that bound to the sis-inducible element and included STAT1 and STAT3, The cell response to IL-10 characteristically differed from that to IL-2/IL-15, IL-4, and interferon gamma. The signaling capabilities of the IL-10R for activating specific STAT proteins and inducing gene transcription were defined by reconstitution of receptor functions in transfected tissue culture cells, COS-1 cells, co-expressing the human IL-10R and individual STAT proteins, confirmed a preference of the IL-10R for STAT3 and STAT1, Unlike many hematopoietin receptors, the IL-10R did not detectably activate STAT5, The IL-10R, together with reporter gene constructs containing different IL-6-responsive gene elements, reconstituted in hepatoma cells an induction of transcription by IL-10 that was comparable to that by IL-6. This regulation could not be appreciably modified by enhanced expression of STAT proteins, The similar actions of IL-10R and IL GR on the induction of endogenous IL-6-responsive genes were demonstrated in hepatoma cells stably expressing the IL-10R. These receptor functions required the presence of the box 3 motifs, as shown by the analysis of the mouse IL-10R constructs containing progressively truncated cytoplasmic domains, The data demonstrate that the IL-10R, unlike other members of the interferon receptor family, is highly effective in recruiting the signaling pathways of IL-6-type cytokine receptors.
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收藏
页码:13968 / 13975
页数:8
相关论文
共 53 条
  • [41] INHIBITION BY INTERLEUKIN-10 OF INDUCIBLE CYCLOOXYGENASE EXPRESSION IN LIPOPOLYSACCHARIDE-STIMULATED MONOCYTES - ITS UNDERLYING MECHANISM IN COMPARISON WITH INTERLEUKIN-4
    NIIRO, H
    OTSUKA, T
    TANABE, T
    HARA, S
    KUGA, S
    NEMOTO, Y
    TANAKA, Y
    NAKASHIMA, H
    KITAJIMA, S
    ABE, M
    NIHO, Y
    [J]. BLOOD, 1995, 85 (12) : 3736 - 3745
  • [42] EFFECT OF IL-2 ON IMMUNOGLOBULIN PRODUCTION BY ANTI-CD40-ACTIVATED HUMAN B-CELLS - SYNERGISTIC EFFECT WITH IL-10 AND ANTAGONISTIC EFFECT WITH IL-4
    NONOYAMA, S
    FARRINGTON, ML
    OCHS, HD
    [J]. CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1994, 72 (03): : 373 - 379
  • [43] STRUCTURE AND ACUTE-PHASE REGULATION OF THE RAT ALPHA-2-MACROGLOBULIN GENE
    NORTHEMANN, W
    SHIELS, BR
    BRACIAK, TA
    HANSON, RW
    HEINRICH, PC
    FEY, GH
    [J]. BIOCHEMISTRY, 1988, 27 (26) : 9194 - 9203
  • [44] RICHARDS CD, 1992, J IMMUNOL, V148, P1731
  • [45] RIPPERGER JA, 1995, J BIOL CHEM, V270, P29998, DOI 10.1074/jbc.270.50.29998
  • [46] A COMMON NUCLEAR SIGNAL-TRANSDUCTION PATHWAY ACTIVATED BY GROWTH-FACTOR AND CYTOKINE RECEPTORS
    SADOWSKI, HB
    SHUAI, K
    DARNELL, JE
    GILMAN, MZ
    [J]. SCIENCE, 1993, 261 (5129) : 1739 - 1744
  • [47] INTERFERON ACTIVATION OF THE TRANSCRIPTION FACTOR STAT91 INVOLVES DIMERIZATION THROUGH SH2-PHOSPHOTYROSYL PEPTIDE INTERACTIONS
    SHUAI, K
    HORVATH, CM
    HUANG, LHT
    QURESHI, SA
    COWBURN, D
    DARNELL, JE
    [J]. CELL, 1994, 76 (05) : 821 - 828
  • [48] CHOICE OF STATS AND OTHER SUBSTRATES SPECIFIED BY MODULAR TYROSINE-BASED MOTIFS IN CYTOKINE RECEPTORS
    STAHL, N
    FARRUGGELLA, TJ
    BOULTON, TG
    ZHONG, Z
    DARNELL, JE
    YANCOPOULOS, GD
    [J]. SCIENCE, 1995, 267 (5202) : 1349 - 1353
  • [49] CHARACTERIZATION OF RECOMBINANT EXTRACELLULAR DOMAIN OF HUMAN INTERLEUKIN-10 RECEPTOR
    TAN, JC
    BRAUN, S
    RONG, H
    DIGIACOMO, R
    DOLPHIN, E
    BALDWIN, S
    NARULA, SK
    ZAVODNY, PJ
    CHOU, CC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (21) : 12906 - 12911
  • [50] CYTOKINE SIGNALING THROUGH NONRECEPTOR PROTEIN-TYROSINE KINASES
    TANIGUCHI, T
    [J]. SCIENCE, 1995, 268 (5208) : 251 - 255