Skip to main content
SpringerLink
Log in

Thec-kit receptor transduces the stem cell factor-triggered growth signal in murine interleukin-3-dependent cell line

  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

The stem cell factor is a glycoprotein hormone which regulates the proliferation and differentiation of primitive hematopoietic cells through its interaction with a tyrosine kinase transmembrane receptor which is encoded by thec-kit proto-oncogene. To examine whether a murinec-kit receptor can be functional in murine interleukin-3 (mlL-3)-dependent hematopoietic cell line, we introduced the murinec-kit cDNA into mlL-3-dependent pro-B cell line Ba/F3. One of the resulting clones, Ba/F3 clone BF-K96, expressed the 140 kDa protein recognized by anti-c-kit monoclonal antibody and the expressedc-kit receptor protein on the cell surface bound to a radiolabeled soluble form of murine stem cell factor (mSCF) with high affinity. BF-K96 clone expressing thec-kit receptor could proliferate in response to mSCF in the absence of mlL-3. The cell clone could also grow in co-culture with mouse 3T3 cells which are endogeneously expressing a membrane-associated type of mSCF on their cell surfaces. These findings demonstrate that thec-kit receptor expressed on mlL-3-dependent hematopoietic cell line Ba/F3 transduce the mSCF-dependent growth signal, indicating that established cell clone will provide a unique cellular system for the study of SCF/c-kit signal transduction mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

SCF:

stem cell factor

IL:

interleukin

CSF:

colony stimulating factor

IMDM:

Iscove's Modified Dulbecco's Medium

DME:

Dulbecco's Modified Eagle's Medium

FCS:

fetal calf serum

PCR:

polymerase chain reaction

EDTA:

ethylenediaminetetra-acetic acid; sodium dodecyl sulfate

References

  • Alai M, Mui AL-F, Culter RL, Bustelo XR, Barbacid M, and Krystal, G (1992) Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hematopoietic cells. J. Biol. Chem. 267: 18021–18025.

    Google Scholar 

  • Anderson DM, Lyman SD, Baird A, Wiganll JM, Eisenman J, Rauch C, March CJ, Boswell HS, Gimpel SD, Cosman D, Williams DE (1990) Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell 63: 235–243.

    Google Scholar 

  • Arai K, Lee F, Muyajima A, Miyatake S, Arai N, Yokota T: Cytokines: Coordinators of immune and inflammatory responses (1990) Annu. Rev. Biochem. 59: 783–836.

    Google Scholar 

  • Bernstein ID, Andrews RG, and Zsebo KM (1991) Recombinant human stem cell factor enhances the formation of colonies by CD34+1 and CD34+1lin− cells, and the generation of colony-forming cell progeny from CD34+1lin− cells cultured with interleukin-3, granulocyte-colony stimulating factor, or granulocyte-macrophage colony stimulating factor. Blood 77: 2316–2321.

    Google Scholar 

  • Blume-Lensen P, Cleasson-Welsh L, Siegbahn A, Zsebo KM, Westermark B, and Heldin CH (1991) Activation of the humanc-kit product by ligand-induced dimerization mediates circular actin reorganization and chemotaxis. EMBO J. 10: 4121–4128.

    Google Scholar 

  • Chabot B, Stephanson DA, Chapman DA, Besmer P, and Bernstein A (1988) The proto-oncogenec-kit encoding a transmembrane tyrosine kinase receptor maps to the mouseW locus. Naature 335: 88–89.

    Google Scholar 

  • Dexter TM, Garland J, Scott D, Scolnick E, and Metcalf D (1980) Growth of factor-dependent hematopoietic precusor cell lines. J. Exp. Med. 152: 1036–1047.

    Google Scholar 

  • Flanagan JG and Leder P (1990) Thec-kit ligand; a cell surface molecule altered in Steel mutant fibroblasts. cell 63: 185–194

    Google Scholar 

  • Flanagan JG, Chan DC, and Leder P (1991) Transmembrane form of thec-kit ligand growth factor is determined by alternative splicing and missing in theSl dmutant. Cell 64: 1025–1035.

    Google Scholar 

  • Geissler EN, Ryan MA, and Houseman DE (1988) The dominant white spotting (W) locus of the mouse encodes thec-kit protooncogene. Cell 55: 185–192.

    Google Scholar 

  • Hendrie PC, Miyazawa K, Yang YC, Langefeld CD, Broxmeyer HE (1991) Mast cell growth factor (c-kit ligand) enhances cytokine stimulation of proliferation of the human factor-dependent cell line, MO7e. Exp. Hemotol. 19: 1031–1037.

    Google Scholar 

  • Huang E, Nocka K, Beier DR, Chu TY, Buck J, Lahm H-W, Wellner D, Leder P, and Besmer P (1990) The hematopoietic growth factor KL is encoded by theSl locus and is the ligand of thec-kit receptor, the gene product of theW locus. Cell 63: 225–233.

    Google Scholar 

  • Hunter WM and Greenwood FC (1962) Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature 194: 495–496.

    Google Scholar 

  • Lev S, Yarden Y, and Givol D (1992) Dimerization and activation of thec-kit receptor by monovalent and bivalent binding of the stem cell factor. J. Biol. Chem. 267: 15970–15977.

    Google Scholar 

  • Liu Y-C, Kawagishi M, Mikayama T, Inagaki M, Takeuchi T, and Ohashi H (1993) Processing of a fusion protein by endoproteinase in COS-1 cells for secretion of mature peptide by using a chimetric expression vector. Proc Natl. Acad. Sci. U.S.A. 90: 8957–8961.

    Google Scholar 

  • Lu HS, Clogston CL, Wpypch J, Parker VP, Lee TD, Swiderek K, Baltera RF, Patel AC, Chang DC, Brankow DW, Liu X-D, Ogden SG, Karkare SB, Hu SS, Zsebo KM, and Langley KE (1992) Post-translation processing of membrane-associated recombinant human stem cell factor expressed in Chinese hamster ovary cells. Arch. Biochem. Viophy. 298: 150–158.

    Google Scholar 

  • Martin FH, Sugga SV, Langley KE, Lu HS, Ting J, Okino KH, Morris CF, McNiece IK, Jacobsen FW, Mendiaz EA, Birkett NC, Smith KA, Johnson MJ, Parker VP, Flores JC, Patel AC, Fisher E. F, Erjavec HO, Herrera CJ, Wpypch J, Sachdev RK, Pope JA, Leslie I, Wenn D, Lin C-H, RL, Zsebo KM (1990) Primary structure and functional expression of rat and human stem cell factor cDNAs. Cell 63: 203–211.

    Google Scholar 

  • Muyajima A, Kitamura T, Harada N, Yokota T, and Arai K Cytokine receptors and signal transduction (1991) Annu. Rev. Immun. 10: 295–331.

    Google Scholar 

  • McNiece IK, Langley KE, and Zsebo KM (1991) Recombinant human stem cell factor (rhSCF) synergises with GM-SCF, G-CSF, lL-3 and EPO to stimulate human progenitor cells of myeloid and erythroid lineages. Exp. Hematol. 19: 226–231.

    Google Scholar 

  • McNiece IK, Langley KE, and Zsebo KM (1991) The role of recombinant stem cell factor in early B cell development: Synergistic interaction with IL-7. J. Immunol. 146: 3785–3790.

    Google Scholar 

  • Nocha K, Buck J, Levi E, and Bermer P. (1990) Candidate lig- and for thec-kit transmembrane tyrosine kinase receptor KL, a tibroblast-derived growth factor stimulates mast cells and erythroid progenitors. EMBO J 9: 3287–3294.

    Google Scholar 

  • Ogawa M, Matsuzaki Y, Nishikawa S, Hayashi S, Kunisada T, Sudo, T, Kina T, Nakauchi H, and Nishikawa S (1991) Expression and function ofc-kit in hematopoietic progenitor cells. J. Exp. Med. 174: 63–71.

    Google Scholar 

  • Ornitz DM and Leder P (1992) Ligand specificity and heparindependence of fibroblast growth factor receptors 1 and 3. J. Biol. Chem. 267: 16305–16311.

    Google Scholar 

  • Palacios R and Steinmetz M (1985) IL-3-dependent mouse clones that express B-220 surface antigen; contain 1g genes in germ-line configulation, and generation of B lymphocytesin vivo. Cell 41: 727–734.

    Google Scholar 

  • Qiu F, Ray P, Brown K, Barker PE, Jhanwar S, Ruddle FH, and Besmer P (1988) Primary structure ofc-kit: relationship with CSF-1/PDGF receptor kinase family-oncogenic activation ofv-kit involves deletion of extracellular domain and C terminus. EMBO J 7: 1003–1011.

    Google Scholar 

  • Rossner MT, McArthur GA, Gough NM, and Metcalf D (1993) Fetal liver kinase 2 catalytic domain can deliver a proliferative signal in factor-dependent hematopoietic cells. Exp. hematol. 21: 1147.

    Google Scholar 

  • Ruden TV and Wagner EF (1988) Expression of functional human EGF receptor on murine bone marrow cells. EMBO J 7: 2749–2756.

    Google Scholar 

  • Russell ES (1979) Hereditary Anemias of the mouse: a review for geneticists. Adv. Genet. 20: 357–459.

    Google Scholar 

  • Shibuya H, Yoneyama M, Ninomiya-Tsuji J, Matsumoto K, and Taniguchi T (1992) IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role forcmyc. Cell 70: 57–67.

    Google Scholar 

  • Ullrich A and Schlessinger J (1990) Signal transduction by receptors with tyrosine kinase activity. Cell 61: 203–212.

    Google Scholar 

  • Williams DE, Eisenman J, Baird A, Rauch C, Van Ness K, March CJ, Park LS, Martin U, Mochizuki DY, Boswell HS, Burgess GS, Cosman D, and Lyman SD (1990) Identification of a ligand for thec-kit proto-oncogene. Cell 63: 167–174.

    Google Scholar 

  • Zsebo KM, Wypych J, NcNiece IK, Lu HS, Smith KA, Karkare SB, Sachdev RK, Yunschenkoff VN, Birkett NC, Williams LR, Satyagal VN, Tung W, Bosselman RA, Mendiaz EA, and Langley KE (1990) Identification, purification, and biological characterization of hemetopoietic stem cell factor from Buffalo rat liver-conditioned medium. Cell 63: 195–201.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., 1-2-2, Souja-machi, 371, Maebashi Gunma, Japan

    Hideya Ohashi, Rie Kameda, Mitsuo Nishikawa, Mayumi Kawagishi & Yun-Cai Liu

Authors
  1. Hideya Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rie Kameda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitsuo Nishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mayumi Kawagishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun-Cai Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ohashi, H., Kameda, R., Nishikawa, M. et al. Thec-kit receptor transduces the stem cell factor-triggered growth signal in murine interleukin-3-dependent cell line. Cytotechnology 16, 27–35 (1994). https://doi.org/10.1007/BF00761776

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00761776

Keywords

Search

Navigation