• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1997 Fiscal Year Final Research Report Summary

Regulation of Cell proliferation by GM-CSF

Research Project

Project/Area Number 08680678
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

WATANABE Sumiko  The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (60240735)

Project Period (FY) 1996 – 1997
KeywordsGM-CSF / receptor / signal trancduction / proliferation / STAT5
Research Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces various functions including the proliferation and differentiation of a broad rango of hematopoietic cells. We reported that at least two distinct pathways are involved in human GM-CSF receptor signaling both of which require the box 1 region of the common beta (betac) subunit. This region is essential for the activation of JAK2, which is necessary for all the biological functions of GM-CSF.Activation of JAK2 by GM-CSF leads to rapid tyrosine phosphorylation of cellular proteins, including the betac. However, the siguificance of the betac phosphorylation in regards to the regulation of signaling molecules and the expression of GM-CSF function is less well understood. Here we investigated the role of cytoplasmic tyrosine residues of the betac by using a series of betac mutants expressed in murine BA/F3 cells. A mutant betac with all eight cytoplasmic tyrosines converted to phenylalanine (Fall) activated JAK2, but not SHP-2, MAPK cascades, STAT5 or c-fos promoter in BA/F3 cells, nor did it effectively induce proliferation. Adding back each tyrosine to Fall revealed that Tyr577, Tyr612 and Tyr695 are involved in the activation of SHP-2, MAPK cascades and c-fos transcription, while every tyrosine, particularly Tyr612, Tyr695, Tyr750 and Tyr806, facilitated STAT5 activation. Impaired growth was also reatored, at least partly, by any of the tyrosines. These results provide evidence that betac tyrosines possess distinct yet overlapping functions to activate multiple signaling pathways induced by GM-CSF.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Itoh, T.et al.: "Definition of the pole of tyrosine residues of the common β subunit regulating multiple signaling pathwors of GM-CSF" Mol.Cell.Biol.18・2. 742-752 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, S.et al.: "Characterigation of eis-acting signals regulating early growth response 1 and c-tos promotes thioyh GM-CSFR in BA/F3 cells." Blood. 89. 1197-1206 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuda, Y.et al.: "human nulocyto-macrophage cdony-stimulating factor (hGM-CSF)induces inhibition of intrathymic I-cell development in hGM-CSF receptor transgenic mice." Blood. 89. 1349-1356 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Muto, A.et al.: "The β subunit of hGM-CSF R foms a homodimer and is aetivated ky association with the α subuint." J.Exp.Med.183. 1911-1916 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh, T. et al.: "GM-CSF provokes RAS activation and transcuption of c-fos throngh different modes of signaling." J.Biol.Chem.271. 7587-7592 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, S.: "JAKα is essential fr activation of c-fos and c-myc promoters and cell proliferahl thcongh the hGM-CSFR in BA/F3 cells." J.Biol.Chem.271. 12681-12686 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh, T., Liu, R., Yokota, T., Arai, K.and Watanabe, S: "Definition of the role of tyrosine residues of the common beta subunit regulating multiple signaling pathways of Granulocyto Macrophage Colony Stimulating Factor recepter" Mol.Cell.Biol. 18,2. 742-752 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, S., Kubota, H., Sakamoto, M.K.and Arai, K: "Characterization of cis-acting sequences and trans-acting signals regulating early growth response 1 (egr-1) and c-fos promoters through the granulocyte-macrophage colony-stimulating factor recepter in BA/F3 cells" Blood. 89. 1197-1206 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasuda, Y., Nishijima, I., Watanabe, S., Arai, K., Zlotonik, A.and Moore, T.A: "Human granulocyto-macrophage colony-stimulating factor (hGM-CSF) induces inhibition of intrathymic T-cell development in hGM-CSF receptor transgenic mice" Blood. 89. 1349-1356 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Muto, A., Watanabe, S., Miyajima, A., Yokota, T.and Arai, K: "The beta subunit of human GM-CSF receptor forms a homodimer and is activated by association with the alpha subunit" J.Exp.Med. 183. 1911-1916 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh, T., Muto, A., Watanabe, S.and Arai, K: "Granulocyte-macrophage colony-stimulating factor provokes RAS activation and transcription of c-fos through different modes of signaling" J.Biol.Chem. 271. 7587-7592 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, S., Itoh, T.and Arai, K: "JAK2 is essential for activation of c-fos and c-myc promoters and cell proliferation through the human granulocyte-macrophage colony stimulating factor (GM-CSF) receptor in BA/F3 cells" J.Biol.Chem. 271. 12681-12686 (1996)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1999-03-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi