p56dok-2 as a cytokine-inducible inhibitor of cell proliferation and signal transduction

被引:67
作者
Suzu, S
Tanaka-Douzono, M
Nomaguchi, K
Yamada, M
Hayasawa, H
Kimura, F
Motoyoshi, K [1 ]
机构
[1] Natl Def Med Coll, Dept Internal Med 3, Tokorozawa, Saitama 3598513, Japan
[2] Morinaga Milk Ind Co Ltd, Biochem Res Lab, Kanagawa 2288583, Japan
关键词
cell proliferation; cytokine; Dok-R; FRIP; p56(dok-2);
D O I
10.1093/emboj/19.19.5114
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
p56(dok-2) acts as a multiple docking protein downstream of receptor or non-receptor tyrosine kinases. However, the role of p56(dok-2) in biological functions of cells is not clear. We found that transcription of the p56(dok-2) gene in macrophages was increased markedly in response to cytokines such as macrophage colony-stimulating factor (M-CSF), granulocyte/macrophage-CSF and interleukin-3 (IL-3), Forced expression of p56dok-2 inhibited M-CSF-, granulocyte-CSF-, IL-3- and stem cell factor-induced proliferation of myeloid leukemia cells, M-NFS-60, The p56(dok-2)-overexpressing cells showed an impaired induction of c-myc but not of c-jun, junB or c-fos when stimulated with M-CSF, Consistent with these results, the peritoneal cavity of the hairless (hr/hr) strain of mutant mice, whose cells expressed less p56(dok-2) than wild-type mice, contained more macrophages than that of +/hr mice. Moreover, the inhibition of endogenous p56(dok-2) expression in macrophage-like tumor cells, J774A.1, by stable expression of antisense p56(dok-2) mRNA accelerated cell proliferation. The study identifies a novel role for p56dok-2 as a molecule that negatively regulates signal transduction and cell proliferation mediated by cytokines in a feedback loop.
引用
收藏
页码:5114 / 5122
页数:9
相关论文
共 54 条
[1]   SEQUENCE REQUIREMENTS FOR BINDING OF SRC FAMILY TYROSINE KINASES TO ACTIVATED GROWTH-FACTOR RECEPTORS [J].
ALONSO, G ;
KOEGL, M ;
MAZURENKO, N ;
COURTNEIDGE, SA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (17) :9840-9848
[2]   MYC BUT NOT FOS RESCUE OF PDGF SIGNALING BLOCK CAUSED BY KINASE INACTIVE SRC [J].
BARONE, MV ;
COURTNEIDGE, S .
NATURE, 1995, 378 (6556) :509-512
[3]   Interactions of p62dok with p210bcr-abl and Bcr-Abl-associated proteins [J].
Bhat, A ;
Johnson, KJ ;
Oda, T ;
Corbin, AS ;
Druker, BJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (48) :32360-32368
[4]   STRUCTURE AND EXPRESSION OF THE HAIRLESS GENE OF MICE [J].
CACHONGONZALEZ, MB ;
FENNER, S ;
COFFIN, JM ;
MORAN, C ;
STOYE, JP ;
BEST, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7717-7721
[5]   p62(dok): A constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells [J].
Carpino, N ;
Wisniewski, D ;
Strife, A ;
Marshak, D ;
Kobayashi, R ;
Stillman, B ;
Clarkson, B .
CELL, 1997, 88 (02) :197-204
[6]   Expression of c-Myc in response to colony-stimulating factor-1 requires mitogen-activated protein kinase kinase-1 [J].
Cheng, M ;
Wang, D ;
Roussel, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6553-6558
[7]  
Cong F, 1999, MOL CELL BIOL, V19, P8314
[8]   Src-related protein tyrosine kinases in hematopoiesis [J].
Corey, SJ ;
Anderson, SM .
BLOOD, 1999, 93 (01) :1-14
[9]   ACTIVATION OF SRC FAMILY KINASES BY COLONY STIMULATING FACTOR-I, AND THEIR ASSOCIATION WITH ITS RECEPTOR [J].
COURTNEIDGE, SA ;
DHAND, R ;
PILAT, D ;
TWAMLEY, GM ;
WATERFIELD, MD ;
ROUSSEL, MF .
EMBO JOURNAL, 1993, 12 (03) :943-950
[10]  
Davila DR., 1997, TOXICOL ECTOTOXICOL, V4, P5