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. 1991 Oct 15;88(20):9026–9030. doi: 10.1073/pnas.88.20.9026

A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit.

W Matthews 1, C T Jordan 1, M Gavin 1, N A Jenkins 1, N G Copeland 1, I R Lemischka 1
PMCID: PMC52644  PMID: 1717995

Abstract

We have cloned a receptor tyrosine kinase cDNA, designated fetal liver kinase 1 (Flk-1), from mouse cell populations enriched for hematopoietic stem and progenitor cells. Sequence analysis of this clone reveals strong homology to the c-Kit subfamily of receptor kinases, and in particular to the Flt gene product. Chromosomal mapping shows that the Flk-1, Kit, and Pdgfra genes are closely linked. Flk-1 mRNA is expressed in primitive and more mature hematopoietic cells as well as in a wide variety of nonhematopoietic tissues.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  2. Chabot B., Stephenson D. A., Chapman V. M., Besmer P., Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988 Sep 1;335(6185):88–89. doi: 10.1038/335088a0. [DOI] [PubMed] [Google Scholar]
  3. Copeland N. G., Jenkins N. A. Development and applications of a molecular genetic linkage map of the mouse genome. Trends Genet. 1991 Apr;7(4):113–118. doi: 10.1016/0168-9525(91)90455-y. [DOI] [PubMed] [Google Scholar]
  4. Dexter T. M., Spooncer E. Growth and differentiation in the hemopoietic system. Annu Rev Cell Biol. 1987;3:423–441. doi: 10.1146/annurev.cb.03.110187.002231. [DOI] [PubMed] [Google Scholar]
  5. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Geissler E. N., Ryan M. A., Housman D. E. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988 Oct 7;55(1):185–192. doi: 10.1016/0092-8674(88)90020-7. [DOI] [PubMed] [Google Scholar]
  7. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  8. Hill R. E., Jones P. F., Rees A. R., Sime C. M., Justice M. J., Copeland N. G., Jenkins N. A., Graham E., Davidson D. R. A new family of mouse homeo box-containing genes: molecular structure, chromosomal location, and developmental expression of Hox-7.1. Genes Dev. 1989 Jan;3(1):26–37. doi: 10.1101/gad.3.1.26. [DOI] [PubMed] [Google Scholar]
  9. Ikuta K., Kina T., MacNeil I., Uchida N., Peault B., Chien Y. H., Weissman I. L. A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell. 1990 Sep 7;62(5):863–874. doi: 10.1016/0092-8674(90)90262-d. [DOI] [PubMed] [Google Scholar]
  10. Jenkins N. A., Copeland N. G., Taylor B. A., Lee B. K. Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus. J Virol. 1982 Jul;43(1):26–36. doi: 10.1128/jvi.43.1.26-36.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jordan C. T., McKearn J. P., Lemischka I. R. Cellular and developmental properties of fetal hematopoietic stem cells. Cell. 1990 Jun 15;61(6):953–963. doi: 10.1016/0092-8674(90)90061-i. [DOI] [PubMed] [Google Scholar]
  12. Matsui T., Heidaran M., Miki T., Popescu N., La Rochelle W., Kraus M., Pierce J., Aaronson S. Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science. 1989 Feb 10;243(4892):800–804. doi: 10.1126/science.2536956. [DOI] [PubMed] [Google Scholar]
  13. Matthews W., Jordan C. T., Wiegand G. W., Pardoll D., Lemischka I. R. A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. Cell. 1991 Jun 28;65(7):1143–1152. doi: 10.1016/0092-8674(91)90010-v. [DOI] [PubMed] [Google Scholar]
  14. McKearn J. P., McCubrey J., Fagg B. Enrichment of hematopoietic precursor cells and cloning of multipotential B-lymphocyte precursors. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7414–7418. doi: 10.1073/pnas.82.21.7414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nocka K., Majumder S., Chabot B., Ray P., Cervone M., Bernstein A., Besmer P. Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice--evidence for an impaired c-kit kinase in mutant mice. Genes Dev. 1989 Jun;3(6):816–826. doi: 10.1101/gad.3.6.816. [DOI] [PubMed] [Google Scholar]
  16. Orr-Urtreger A., Avivi A., Zimmer Y., Givol D., Yarden Y., Lonai P. Developmental expression of c-kit, a proto-oncogene encoded by the W locus. Development. 1990 Aug;109(4):911–923. doi: 10.1242/dev.109.4.911. [DOI] [PubMed] [Google Scholar]
  17. Pawson T., Bernstein A. Receptor tyrosine kinases: genetic evidence for their role in Drosophila and mouse development. Trends Genet. 1990 Nov;6(11):350–356. doi: 10.1016/0168-9525(90)90276-c. [DOI] [PubMed] [Google Scholar]
  18. Shibuya M., Yamaguchi S., Yamane A., Ikeda T., Tojo A., Matsushime H., Sato M. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene. 1990 Apr;5(4):519–524. [PubMed] [Google Scholar]
  19. Spangrude G. J., Heimfeld S., Weissman I. L. Purification and characterization of mouse hematopoietic stem cells. Science. 1988 Jul 1;241(4861):58–62. doi: 10.1126/science.2898810. [DOI] [PubMed] [Google Scholar]
  20. Stephenson D. A., Mercola M., Anderson E., Wang C. Y., Stiles C. D., Bowen-Pope D. F., Chapman V. M. Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):6–10. doi: 10.1073/pnas.88.1.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  22. Watson M. E. Compilation of published signal sequences. Nucleic Acids Res. 1984 Jul 11;12(13):5145–5164. doi: 10.1093/nar/12.13.5145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wilks A. F. Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1603–1607. doi: 10.1073/pnas.86.5.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  25. Witte O. N. Steel locus defines new multipotent growth factor. Cell. 1990 Oct 5;63(1):5–6. doi: 10.1016/0092-8674(90)90280-r. [DOI] [PubMed] [Google Scholar]
  26. von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. doi: 10.1111/j.1432-1033.1983.tb07424.x. [DOI] [PubMed] [Google Scholar]

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