JAK2 is essential for activation of c-fos and c-myc promoters and cell proliferation through the human granulocyte-macrophage colony-stimulating factor receptor in BA/F3 cells

被引:109
作者
Watanabe, S [1 ]
Itoh, T [1 ]
Arai, K [1 ]
机构
[1] UNIV TOKYO,INST MED SCI,DEPT MED & DEV BIOL,MINATO KU,TOKYO 108,JAPAN
关键词
D O I
10.1074/jbc.271.21.12681
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
Interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to activate JAK2 in various cells, but the role of JAK2 in IL-3 or GM-CSF receptor signal transduction is largely unknown. We have now examined the role of JAK2 in GM-CSF-induced signaling events in BA/F3 cells. In BA/F3 cells expressing hGMR, activation of JAK2 by hGM-CSF requires the box1 region of hGMR beta. Dominant negative JAK2 (Delta JAK2), which lacked the kinase domain suppressed mIL-3- or hGM-CSF-induced c-fos promoter activation as well as c-myc promoter activation/cell proliferation, thereby suggesting that JAK2 is involved in the signaling of both pathways. Further analyses of the role of JAK2 in c-fos gene activation in BA/F3 cells expressing hGMR revealed that Delta JAK2 inhibited hGM-CSF-induced phosphorylation of Shc and protein tyrosine phosphatase 1D. Within hGMR beta, the several tyrosine residues which exist are related to activation of Shc or protein tyrosine phosphatase 1D, and are phosphorylated in response to hGM-CSF stimulation. In addition, we observed that Delta JAK2 inhibited hGM-CSF-induced phosphorylation of hGMR beta. Taken together, our results suggest that JAK2 activated by the box1 region of hGMR mediates hGM-CSF-induced c-fos promoter activation through phosphorylation of hGMR.
引用
收藏
页码:12681 / 12686
页数:6
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[21]   USE OF THE SILKWORM, BOMBYX-MORI, AND AN INSECT BACULOVIRUS VECTOR FOR HIGH-LEVEL EXPRESSION AND SECRETION OF BIOLOGICALLY-ACTIVE MOUSE INTERLEUKIN-3 [J].
MIYAJIMA, A ;
SCHREURS, J ;
OTSU, K ;
KONDO, A ;
ARAI, K ;
MAEDA, S .
GENE, 1987, 58 (2-3) :273-281
[22]   HEMATOPOIETIC GROWTH-FACTORS ACTIVATE THE TYROSINE PHOSPHORYLATION OF DISTINCT SETS OF PROTEINS IN INTERLEUKIN-3-DEPENDENT MURINE CELL-LINES [J].
MORLA, AO ;
SCHREURS, J ;
MIYAJIMA, A ;
WANG, JYJ .
MOLECULAR AND CELLULAR BIOLOGY, 1988, 8 (05) :2214-2218
[23]   INTERLEUKIN-3, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERLEUKIN-5 TRANSDUCE SIGNALS THROUGH 2 STAT5 HOMOLOGS [J].
MUI, ALF ;
WAKAO, H ;
OFARRELL, AM ;
HARADA, N ;
MIYAJIMA, A .
EMBO JOURNAL, 1995, 14 (06) :1166-1175
[24]   THE PROTEIN-TYROSINE KINASE JAK1 COMPLEMENTS DEFECTS IN INTERFERON-ALPHA/BETA AND INTERFERON-GAMMA SIGNAL-TRANSDUCTION [J].
MULLER, M ;
BRISCOE, J ;
LAXTON, C ;
GUSCHIN, D ;
ZIEMIECKI, A ;
SILVENNOINEN, O ;
HARPUR, AG ;
BARBIERI, G ;
WITTHUHN, BA ;
SCHINDLER, C ;
PELLEGRINI, S ;
WILKS, AF ;
IHLE, JN ;
STARK, GR ;
KERR, IM .
NATURE, 1993, 366 (6451) :129-135
[25]   CRITICAL CYTOPLASMIC REGION OF THE INTERLEUKIN-6 SIGNAL TRANSDUCER GP130 IS CONSERVED IN THE CYTOKINE RECEPTOR FAMILY [J].
MURAKAMI, M ;
NARAZAKI, M ;
HIBI, M ;
YAWATA, H ;
YASUKAWA, K ;
HAMAGUCHI, M ;
TAGA, T ;
KISHIMOTO, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (24) :11349-11353
[26]   INTERLEUKIN-5 AND INTERLEUKIN-3 INDUCE SERINE AND TYROSINE PHOSPHORYLATIONS OF SEVERAL CELLULAR PROTEINS IN AN INTERLEUKIN-5-DEPENDENT CELL-LINE [J].
MURATA, Y ;
YAMAGUCHI, N ;
HITOSHI, Y ;
TOMINAGA, A ;
TAKATSU, K .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 173 (03) :1102-1108
[27]   ACTIVATION OF JAK2 KINASE MEDIATED BY THE INTERLEUKIN-6 SIGNAL TRANSDUCER GP130 [J].
NARAZAKI, M ;
WITTHUHN, BA ;
YOSHIDA, K ;
SILVENNOINEN, O ;
YASUKAWA, K ;
IHLE, JN ;
KISHIMOTO, T ;
TAGA, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (06) :2285-2289
[28]   A NOVEL TRANSFORMING PROTEIN (SHC) WITH AN SH2 DOMAIN IS IMPLICATED IN MITOGENIC SIGNAL TRANSDUCTION [J].
PELICCI, G ;
LANFRANCONE, L ;
GRIGNANI, F ;
MCGLADE, J ;
CAVALLO, F ;
FORNI, G ;
NICOLETTI, I ;
GRIGNANI, F ;
PAWSON, T ;
PELICCI, PG .
CELL, 1992, 70 (01) :93-104
[29]   JAK2 ASSOCIATES WITH THE BETA(C) CHAIN OF THE RECEPTOR FAR GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, AND ITS ACTIVATION REQUIRES THE MEMBRANE-PROXIMAL REGION [J].
QUELLE, FW ;
SATO, N ;
WITTHUHN, BS ;
INHORN, RC ;
EDER, M ;
MIYAJIMA, A ;
GRIFFIN, JD ;
IHLE, JN .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (07) :4335-4341
[30]  
QUELLE FW, 1995, MOL CELL BIOL, V15, P3336