This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kuribara, R.
Right arrow Articles by Inaba, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuribara, R.
Right arrow Articles by Inaba, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 1999, p. 2754-2762, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Two Distinct Interleukin-3-Mediated Signal Pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, Regulate the Survival of Murine Pro-B Lymphocytes

Ryoko Kuribara,1,2 Taisei Kinoshita,3 Atsushi Miyajima,3 Tetsuharu Shinjyo,1 Takao Yoshihara,4 Takeshi Inukai,4 Keiya Ozawa,1,2 A. Thomas Look,4 and Toshiya Inaba1,*

Departments of Molecular Biology1 and Hematology,2 Jichi Medical School, Tochigi 329-0498, and Institute of Molecular and Cellular Bioscience, the University of Tokyo, Tokyo 174,3 Japan, and Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 381054

Received 15 July 1998/Returned for modification 6 September 1998/Accepted 22 January 1999

Hematopoietic cells require cytokine-initiated signals for survival as well as proliferation. The pathways that transduce these signals, ensuring timely regulation of cell fate genes, remain largely undefined. The NFIL3 (E4BP4) transcription factor, Bcl-xL, and constitutively active mutants of components in Ras signal transduction pathways have been identified as key regulation proteins affecting murine interleukin-3 (IL-3)-dependent cell survival. Here we show that expression of NFIL3 is regulated by oncogenic Ras mutants through both the Raf-mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. NFIL3 inhibits apoptosis without affecting Bcl-xL expression. By contrast, Bcl-xL levels are regulated through the membrane proximal portion in the cytoplasmic domain of the receptor (beta c chain), which is shared by IL-3 and granulocyte-macrophage colony-stimulating factor. Activation of either pathway alone is insufficient to ensure cell survival, indicating that multiple independent signal transduction pathways mediate the survival of developing B-lymphoid cells.

* Corresponding author. Mailing address: Department of Molecular Biology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Tochigi 329-0498, Japan. Phone: 81-285-58-7402. Fax: 81-285-44-8675. E-mail: tinaba{at}jichi.ac.jp.

Molecular and Cellular Biology, April 1999, p. 2754-2762, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Alvarez, J. V., Febbo, P. G., Ramaswamy, S., Loda, M., Richardson, A., Frank, D. A. (2005). Identification of a Genetic Signature of Activated Signal Transducer and Activator of Transcription 3 in Human Tumors. Cancer Res. 65: 5054-5062 [Abstract] [Full Text]  
  • Inukai, T., Inaba, T., Dang, J., Kuribara, R., Ozawa, K., Miyajima, A., Wu, W., Look, A. T., Arinobu, Y., Iwasaki, H., Akashi, K., Kagami, K., Goi, K., Sugita, K., Nakazawa, S. (2005). TEF, an antiapoptotic bZIP transcription factor related to the oncogenic E2A-HLF chimera, inhibits cell growth by down-regulating expression of the common {beta} chain of cytokine receptors. Blood 105: 4437-4444 [Abstract] [Full Text]  
  • Peeters, P. J., Gohlmann, H. W., Van den Wyngaert, I., Swagemakers, S. M., Bijnens, L., Kass, S. U., Steckler, T. (2004). Transcriptional Response to Corticotropin-Releasing Factor in AtT-20 Cells. Mol. Pharmacol. 66: 1083-1092 [Abstract] [Full Text]  
  • Greenbaum, S., Lazorchak, A. S., Zhuang, Y. (2004). Differential Functions for the Transcription Factor E2A in Positive and Negative Gene Regulation in Pre-B Lymphocytes. J. Biol. Chem. 279: 45028-45035 [Abstract] [Full Text]  
  • Junghans, D., Chauvet, S., Buhler, E., Dudley, K., Sykes, T., Henderson, C. E. (2004). The CES-2-related transcription factor E4BP4 is an intrinsic regulator of motoneuron growth and survival. Development 131: 4425-4434 [Abstract] [Full Text]  
  • Ozkurt, I. C., Pirih, F. Q., Tetradis, S. (2004). Parathyroid Hormone Induces E4bp4 Messenger Ribonucleic Acid Expression Primarily through Cyclic Adenosine 3',5'-Monophosphate Signaling in Osteoblasts. Endocrinology 145: 3696-3703 [Abstract] [Full Text]  
  • Kuribara, R., Honda, H., Matsui, H., Shinjyo, T., Inukai, T., Sugita, K., Nakazawa, S., Hirai, H., Ozawa, K., Inaba, T. (2004). Roles of Bim in Apoptosis of Normal and Bcr-Abl-Expressing Hematopoietic Progenitors. Mol. Cell. Biol. 24: 6172-6183 [Abstract] [Full Text]  
  • Matsunaga, T., Inaba, T., Matsui, H., Okuya, M., Miyajima, A., Inukai, T., Funabiki, T., Endo, M., Look, A. T., Kurosawa, H. (2004). Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein. Blood 103: 3185-3191 [Abstract] [Full Text]  
  • Guthridge, M. A., Barry, E. F., Felquer, F. A., McClure, B. J., Stomski, F. C., Ramshaw, H., Lopez, A. F. (2004). The phosphoserine-585-dependent pathway of the GM-CSF/IL-3/IL-5 receptors mediates hematopoietic cell survival through activation of NF-{kappa}B and induction of bcl-2. Blood 103: 820-827 [Abstract] [Full Text]  
  • Lund, R., Aittokallio, T., Nevalainen, O., Lahesmaa, R. (2003). Identification of Novel Genes Regulated by IL-12, IL-4, or TGF-{beta} during the Early Polarization of CD4+ Lymphocytes. J. Immunol. 171: 5328-5336 [Abstract] [Full Text]  
  • Szuplewski, S., Kottler, B., Terracol, R. (2003). The Drosophila bZIP transcription factor Vrille is involved in hair and cell growth. Development 130: 3651-3662 [Abstract] [Full Text]  
  • Ozkurt, I. C., Tetradis, S. (2003). Parathyroid Hormone-induced E4BP4/NFIL3 Down-regulates Transcription in Osteoblasts. J. Biol. Chem. 278: 26803-26809 [Abstract] [Full Text]  
  • Yu, Y.-L., Chiang, Y.-J., Yen, J. J. Y. (2002). GATA Factors Are Essential for Transcription of the Survival Gene E4bp4 and the Viability Response of Interleukin-3 in Ba/F3 Hematopoietic Cells. J. Biol. Chem. 277: 27144-27153 [Abstract] [Full Text]  
  • Dijkers, P. F., Birkenkamp, K. U., Lam, E. W.-F., Thomas, N. S. B., Lammers, J.-W. J., Koenderman, L., Coffer, P. J. (2002). FKHR-L1 can act as a critical effector of cell death induced by cytokine withdrawal: protein kinase B-enhanced cell survival through maintenance of mitochondrial integrity. JCB 156: 531-542 [Abstract] [Full Text]  
  • Bae, Y.-S., Kim, Y., Park, J. C., Suh, P.-G., Ryu, S. H. (2002). The synthetic chemoattractant peptide, Trp-Lys-Tyr-Met-Val-D-Met, enhances monocyte survival via PKC-dependent Akt activation. J. Leukoc. Biol. 71: 329-338 [Abstract] [Full Text]  
  • Aldinucci, D., Poletto, D., Gloghini, A., Nanni, P., Degan, M., Perin, T., Ceolin, P., Rossi, F. M., Gattei, V., Carbone, A., Pinto, A. (2002). Expression of Functional Interleukin-3 Receptors on Hodgkin and Reed-Sternberg Cells. Am. J. Pathol. 160: 585-596 [Abstract] [Full Text]  
  • Mitsui, S., Yamaguchi, S., Matsuo, T., Ishida, Y., Okamura, H. (2001). Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes Dev. 15: 995-1006 [Abstract] [Full Text]  
  • Shinjyo, T., Kuribara, R., Inukai, T., Hosoi, H., Kinoshita, T., Miyajima, A., Houghton, P. J., Look, A. T., Ozawa, K., Inaba, T. (2001). Downregulation of Bim, a Proapoptotic Relative of Bcl-2, Is a Pivotal Step in Cytokine-Initiated Survival Signaling in Murine Hematopoietic Progenitors. Mol. Cell. Biol. 21: 854-864 [Abstract] [Full Text]  
  • Rebollo, A., Martinez-A, C. (1999). Ras Proteins: Recent Advances and New Functions. Blood 94: 2971-2980 [Full Text]  
  • Wolfman, J. C., Wolfman, A. (2000). Endogenous c-N-Ras Provides a Steady-state Anti-apoptotic Signal. J. Biol. Chem. 275: 19315-19323 [Abstract] [Full Text]  
  • Nishimura, Y., Tanaka, T. (2001). Calcium-dependent Activation of Nuclear Factor Regulated by Interleukin 3/Adenovirus E4 Promoter-binding Protein Gene Expression by Calcineurin/Nuclear Factor of Activated T Cells and Calcium/Calmodulin-dependent Protein Kinase Signaling. J. Biol. Chem. 276: 19921-19928 [Abstract] [Full Text]  
  • Doi, M., Nakajima, Y., Okano, T., Fukada, Y. (2001). Light-induced phase-delay of the chicken pineal circadian clock is associated with the induction of cE4bp4, a potential transcriptional repressor of cPer2 gene. Proc. Natl. Acad. Sci. USA 98: 8089-8094 [Abstract] [Full Text]  
  • Dijkers, P. F., Birkenkamp, K. U., Lam, E. W.-F., Thomas, N. S. B., Lammers, J.-W. J., Koenderman, L., Coffer, P. J. (2002). FKHR-L1 can act as a critical effector of cell death induced by cytokine withdrawal: protein kinase B-enhanced cell survival through maintenance of mitochondrial integrity. JCB 156: 531-542 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»