![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
S Watanabe, A Muto, T Yokota, A Miyajima and K Arai
Department of Molecular and Developmental Biology, University of Tokyo, Japan.
Granulocyte macrophage colony-stimulating factor (GM-CSF) binds to the high-affinity GM-CSF receptor (GMR) consisting of alpha and beta subunits and induces rapid tyrosine phosphorylation, activation of early response genes, and proliferation of hematopoietic cells. The alpha subunit is the primary cytokine binding component and the beta subunit is required for high-affinity binding as well as for signal transduction. Using tyrosine kinase inhibitors and cytoplasmic deletion mutants of the beta subunit, we obtained evidence that there are at least two distinct pathways downstream of the GMR in BA/F3 cell, one which is essential for proliferation, leads to the c-myc gene activation, and is sensitive to herbimycin and genistein. Activation of this pathway depends on the cytoplasmic region between amino acid positions 455 and 517 of the beta subunit. The second pathway, which leads to activation of c-fos and c-jun genes, is only partially sensitive to herbimycin, is resistant to genistein and depends on the region between amino acid positions 626 and 763 of the beta subunit. Unexpectedly, the c-fos mRNA induction was augmented by genistein. The enhanced expression of c-fos mRNA by genistein also occurred with stimulation with cAMP, PMA, or EGF in NIH3T3 cells. It thus seems likely that genistein affects a common pathway downstream of these signals.
This article has been cited by other articles:
|
|
 |
|
  S. Watanabe, R. Zeng, Y. Aoki, T. Itoh, and K.-i. Arai Initiation of polyoma virus origin-dependent DNA replication through STAT5 activation by human granulocyte-macrophage colony-stimulating factor Blood, March 1, 2001; 97(5): 1266 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Watanabe, Y. Aoki, I. Nishijima, M.-j. Xu, and K.-i. Arai Analysis of Signals and Functions of the Chimeric Human Granuloctye-Macrophage Colony-Stimulating Factor Receptor in BA/F3 Cells and Transgenic Mice J. Immunol., April 1, 2000; 164(7): 3635 - 3644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Liu, T. Itoh, K.-i. Arai, and S. Watanabe Two Distinct Signaling Pathways Downstream of Janus Kinase 2 Play Redundant Roles for Antiapoptotic Activity of Granulocyte-Macrophage Colony-stimulating Factor Mol. Biol. Cell, November 1, 1999; 10(11): 3959 - 3970. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. Tanaka, K. Kaneko, H. Asao, H. Kasai, Y. Endo, T. Fujita, T. Takeshita, and K. Sugamura Possible Involvement of a Novel STAM-associated Molecule "AMSH" in Intracellular Signal Transduction Mediated by Cytokines J. Biol. Chem., July 2, 1999; 274(27): 19129 - 19135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-B. Liu, T. Itoh, K.-i. Arai, and S. Watanabe Constitutive Activation of JAK2 Confers Murine Interleukin-3-independent Survival and Proliferation of BA/F3 Cells J. Biol. Chem., March 5, 1999; 274(10): 6342 - 6349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Mohi, K.-i. Arai, and S. Watanabe Activation and Functional Analysis of Janus Kinase 2 in BA/F3 Cells Using the Coumermycin/Gyrase B System Mol. Biol. Cell, December 1, 1998; 9(12): 3299 - 3308. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Yamashita, S. Watanabe, A. Miyazato, K.-i. Ohya, U. Ikeda, K. Shimada, N. Komatsu, K. Hatake, Y. Miura, K. Ozawa, et al. Tec and Jak2 Kinases Cooperate to Mediate Cytokine-Driven Activation of c-fos Transcription Blood, March 1, 1998; 91(5): 1496 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. I. Rivas, J. Carlos Vera, F. Delgado-Lopez, M. L. Heaney, V. H. Guaiquil, R. H. Zhang, H. I. Scher, I. I. Concha, F. Nualart, C. Cordon-Cardo, et al. Expression of Granulocyte-Macrophage Colony-Stimulating Factor Receptors in Human Prostate Cancer Blood, February 1, 1998; 91(3): 1037 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Asao, Y. Sasaki, T. Arita, N. Tanaka, K. Endo, H. Kasai, T. Takeshita, Y. Endo, T. Fujita, and K. Sugamura Hrs Is Associated with STAM, a Signal-transducing Adaptor Molecule. ITS SUPPRESSIVE EFFECT ON CYTOKINE-INDUCED CELL GROWTH J. Biol. Chem., December 26, 1997; 272(52): 32785 - 32791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jenab and P. L. Morris Transcriptional Regulation of Sertoli Cell Immediate Early Genes by Interleukin-6 and Interferon-{gamma} Is Mediated through Phosphorylation of STAT-3 and STAT-1 Proteins Endocrinology, July 1, 1997; 138(7): 2740 - 2746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Watanabe, H. Kubota, K. M. Sakamoto, and K.-i. Arai Characterization of cis-Acting Sequences and trans-Acting Signals Regulating Early Growth Response 1 and c-fos Promoters Through the Granulocyte-Macrophage Colony-Stimulating Factor Receptor in BA/F3 Cells Blood, February 15, 1997; 89(4): 1197 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Watanabe, T. Itoh, and K.-i. Arai 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 J. Biol. Chem., May 24, 1996; 271(21): 12681 - 12686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Itoh, A. Muto, S. Watanabe, A. Miyajima, T. Yokota, and K.-i. Arai Granulocyte-macrophage Colony-stimulating Factor Provokes RAS Activation and Transcription of c-fos through Different Modes of Signaling J. Biol. Chem., March 29, 1996; 271(13): 7587 - 7592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Watanabe, Y. Ito, A. Miyajima, and K.-i. Arai Granulocyte Macrophage-Colony Stimulating Factor-dependent Replication of Polyoma Virus Replicon in Hematopoietic Cells J. Biol. Chem., April 21, 1995; 270(16): 9615 - 9621. [Abstract] [Full Text] [PDF]
|
|
