Identification of soluble and membrane-bound isoforms of the murine flt3 ligand generated by alternative splicing of mRNAs

S. D. Lyman, L. James, S. Escobar, H. Downey, P. De Vries, I. Brasel, K. Stocking, M. P. Beckmann, Neal G. Copeland, L. S. Cleveland, Nancy A. Jenkins, J. W. Belmont, B. L. Davison

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

We have recently described a novel hematopoietic growth factor, referred to as the flt3 ligand, that stimulates the proliferation of sub-populations of hematopoietic cells that are enriched for stem and progenitor cells. This factor is a transmembrane protein that undergoes proteolytic cleavage to generate a soluble form of the protein. We have isolated additional flt3 ligand isoforms by PCR that contain an extra exon and encode what are predicted to be either a soluble form of the ligand or a longer version of the transmembrane protein. We have also isolated cDNAs from murine T cell libraries that encode an isoform of the flt3 ligand that has an unusual C-terminus. This isoform results from a failure to splice out an intron during mRNA processing. The protein encoded by this cDNA is expressed on the cell surface, where it is biologically active. However, this novel isoform does not appear to give rise to a soluble form of the protein. Regulation of mRNA splicing is likely to control the generation of cell bound or soluble forms of this hematopoietic growth factor. Genetic mapping studies localize the gene encoding the flt3 ligand to the proximal portion of mouse chromosome 7 and to human chromosome 19q13.3.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalOncogene
Volume10
Issue number1
StatePublished - Jan 1 1995

Keywords

  • flt3 ligand
  • Gene location
  • Growth factor
  • Hematopoeisis
  • Tyrosine kinase receptor

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Identification of soluble and membrane-bound isoforms of the murine flt3 ligand generated by alternative splicing of mRNAs'. Together they form a unique fingerprint.

Cite this