INTERLEUKIN-2 SIGNALING INVOLVES THE PHOSPHORYLATION OF STAT PROTEINS

被引:106
作者
FRANK, DA
ROBERTSON, MJ
BONNI, A
RITZ, J
GREENBERG, ME
机构
[1] HARVARD UNIV,SCH MED,DEPT MOLEC GENET & MICROBIOL,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115
[3] DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115
[4] DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115
关键词
TYROSINE PHOSPHORYLATION; CYTOKINE; LYMPHOCYTE; NATURAL KILLER CELL;
D O I
10.1073/pnas.92.17.7779
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
One of the most important cytokines involved in immune response regulation is interleukin 2 (IL-2), a potent activator of the proliferation and function of T lymphocytes and natural killer cells, The mechanisms by which the effects of IL-2 are propagated within cells are not understood, While the binding of IL-2 to its receptor was recently shown to lead to the activation of two kinases, Jak-1 and Jak-3, subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized, Since many cytokines that activate Jak kinases also lead to the tyrosine phosphorylation and activation of members of the Stat family of transcription factors, the ability of IL-2 to trigger Stat phosphorylation was examined. Exposure of activated human T lymphocytes or of a natural killer cell line (NKL) to IL-2 leads to the phosphorylation of Stat1 alpha, Stat1 beta, and Stat3, as well as of two Stat-related proteins, p94 and p95. p94 and p95 share homology with Stat1 at the phosphorylation site and in the Src homology 2 (SH2) domain, but otherwise are immunologically distinct from Stat1, These Stat proteins were found to translocate to the nucleus and to bind to a specific DNA sequence. These findings suggest a mechanism by which IL-2 binding to its receptor may activate specific genes involved in immune cell function.
引用
收藏
页码:7779 / 7783
页数:5
相关论文
共 37 条
[1]   MOLECULAR-CLONING OF APRF, A NOVEL IFN-STIMULATED GENE FACTOR-3 P91-RELATED TRANSCRIPTION FACTOR INVOLVED IN THE GP130-MEDIATED SIGNALING PATHWAY [J].
AKIRA, S ;
NISHIO, Y ;
INOUE, M ;
WANG, XJ ;
WEI, S ;
MATSUSAKA, T ;
YOSHIDA, K ;
SUDO, T ;
NARUTO, M ;
KISHIMOTO, T .
CELL, 1994, 77 (01) :63-71
[2]   CHARACTERIZATION OF A PATHWAY FOR CILIARY NEUROTROPHIC FACTOR SIGNALING TO THE NUCLEUS [J].
BONNI, A ;
FRANK, DA ;
SCHINDLER, C ;
GREENBERG, ME .
SCIENCE, 1993, 262 (5139) :1575-1579
[3]   PREVENTION OF T-CELL ANERGY BY SIGNALING THROUGH THE GAMMA(C) CHAIN OF THE IL-2 RECEPTOR [J].
BOUSSIOTIS, VA ;
BARBER, DL ;
NAKARAI, T ;
FREEMAN, GJ ;
GRIBBEN, JG ;
BERNSTEIN, GM ;
DANDREA, AD ;
RITZ, J ;
NADLER, LM .
SCIENCE, 1994, 266 (5187) :1039-1042
[4]  
COSMAN D, 1993, CYTOKINE, V5, P96
[5]  
EVANS SW, 1987, J BIOL CHEM, V262, P4624
[6]   PROLACTIN INDUCES PHOSPHORYLATION OF TYR694 OF STAT5 (MGF), A PREREQUISITE FOR DNA-BINDING AND INDUCTION OF TRANSCRIPTION [J].
GOUILLEUX, F ;
WAKAO, H ;
MUNDT, M ;
GRONER, B .
EMBO JOURNAL, 1994, 13 (18) :4361-4369
[7]   LYMPHOCYTE-T INTERLEUKIN-2-DEPENDENT TYROSINE PROTEIN-KINASE SIGNAL TRANSDUCTION INVOLVES THE ACTIVATION OF P56LCK [J].
HORAK, ID ;
GRESS, RE ;
LUCAS, PJ ;
HORAK, EM ;
WALDMANN, TA ;
BOLEN, JB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (05) :1996-2000
[8]   AN INTERLEUKIN-4-INDUCED TRANSCRIPTION FACTOR - IL-4 STAT [J].
HOU, JZ ;
SCHINDLER, U ;
HENZEL, WJ ;
HO, TC ;
BRASSEUR, M ;
MCKNIGHT, SL .
SCIENCE, 1994, 265 (5179) :1701-1706
[9]   PHOSPHORYLATION AND ACTIVATION OF THE JAK-3 JANUS KINASE IN RESPONSE TO INTERLEUKIN-2 [J].
JOHNSTON, JA ;
KAWAMURA, M ;
KIRKEN, RA ;
CHEN, YQ ;
BLAKE, TB ;
SHIBUYA, K ;
ORTALDO, JR ;
MCVICAR, DW ;
O'SHEA, JJ .
NATURE, 1994, 370 (6485) :151-153
[10]   MOLECULAR-CLONING OF L-JAK, A JANUS FAMILY PROTEIN-TYROSINE KINASE EXPRESSED IN NATURAL-KILLER-CELLS AND ACTIVATED LEUKOCYTES [J].
KAWAMURA, M ;
MCVICAR, DW ;
JOHNSTON, JA ;
BLAKE, TB ;
CHEN, YQ ;
LAL, BK ;
LLOYD, AR ;
KELVIN, DJ ;
STAPLES, JE ;
ORTALDO, JR ;
OSHEA, JJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (14) :6374-6378