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

2000 Fiscal Year Final Research Report Summary

Jak2-and Lyn-mediated Intracellular Signaling from the Erythropoietin Receptor

Research Project

Project/Area Number 11670984
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MIURA Osamu  Tokyo Medical and Dental University, Department of Hematology/Oncology, Professor, 大学院・医歯学総合研究科, 教授 (10209710)

Project Period (FY) 1999 – 2000
KeywordsErythropoietin / Jak2 / Lyn / CrkL / Rap1
Research Abstract

Erythropoietin (Epo) is a hematopoietic growth factor that regulates the growth and differentiation of erythroid progenitor cells through activation of its specific receptor expressed on the cell surface. The receptor for Epo (EpoR) transduces its signals by activating receptor-associated tyrosine kinases, mainly Jak2 and Lyn, and thereby inducing tyrosine phosphorylation of various signaling molecules including the EpoR itself. We have found that CrkL, an adapter protein implicated in pathogenesis of chronic myelogenous leukemia, is recruited to the EpoR, possibly through interaction between the CrkL SH2 domain and phosphorylated Y-460 in the EpoR cytoplasmic domain, and undergoes tyrosine phosphorylation by receptor-associated Lyn in Epo-stimulated hematopoietic cells. Through its interaction with C3G, a guanine nucleotide exchange factor for the Ras family GTPases, CrkL was found to mediate Epo-induced activation of Ras and Rap1. By using various mutants of these GTPases and other signaling molecules, we have also found that the activation of Rap1 is involved in stimulation of VLA-4 and VLA-5 integrin-mediated adhesion of hematopoietic cells. It was further indicated that phospholipase C-g, known to be activated by the EpoR, may also mediate the Epo-induced Rap1 activation through generation of its second messengers. Together, these data indicate that the EpoR activates Rap1 through recruitment of the CrkL/C3G complex as well as through activation of phospholipase C-g, which results in activation of integrin-mediated hematopoietic cell adhesion.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Nosaka Y,Arai A,Miyasaka N and Miura O: "CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3"J Biol Chem. 274. 30154-62 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arai A,Nosaka Y,Kohsaka H,Miyasaka N and Miura O: "CrkL activates integrin-mediated hematopoietic cell adhesion through the guanine nucleotide exchange factor C3G"Blood. 93. 3713-22 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto K,Shibata F,Miura O,Kamiyama R,Hirosawa S and Miyasaka N: "Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase : Jak2 associates with cytoplasmic membrane- proximal region of interleukin-12 receptor beta 2 via amino-terminus"Biochem Biophys Res Commun. 257. 400-4 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chida D,Miura O,Yoshimura A and Miyajima A: "Role of cytokine signaling molecules in erythroid differentiation of mouse fetal liver hematopoietic cells : functional analysis of signaling molecules by retrovirus-mediated expression"Blood. 93. 1567-78 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arai A,Nosaka Y,Kanda E,Yamamoto K.Miyasaka N,Miura O: "Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of {beta}1 integrin-mediated hematopoietic cell adhesion."J Biol Chem. 276(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Osamu Miura: "Involvement of the CrkL/C3G complex and Rap1 in signaling from the erythropoietin receptor in Molecular Target for Hematological Malignancies and Cancer."Kyushu University Press. 9 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nosaka Y, Arai A, Miyasaka N and Miura O: "CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3"J Biol Chem. 274. 30154-62 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arai A, Nosaka Y, Kohsaka H, Miyasaka N and Miura O: "CrkL activates integrin-mediated hematopoietic cell adhesion through the guanine nucleotide exchange factor C3G"Blood. 93. 3713-22 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto K, Shibata F, Miura O, Kamiyama R, Hirosawa S and Miyasaka N: "Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase : Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus"Biochem Biophys Res Commun. 257. 400-4 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chida D, Miura O, Yoshimura A and Miyajima A: "Role of cytokine signaling molecules in erythroid differentiation of mouse fetal liver hematopoietic cells : functional analysis of signaling molecules by retrovirus-mediated expression"Blood. 93. 1567-78 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arai A, Nosaka Y, Kanda E, Yamamoto K, Miyasaka N, Miura O: "Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of {beta} 1 integrin-mediated hematopoietic cell adhesion."J Biol Chem. 276 (in press). (2001)

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

URL: 

Published: 2002-03-26  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi