Biological control of mast cell growth factor c-kit interactions may be mediated through alternate splicing of mRNAs

Abstract

Mast cell growth factor (MGF) is a newly described hematopoietic growth factor that is a ligand for the c-kit proto-oncogene and is a product of the Sl locus on mouse chromosome 10. This factor and its receptor play key roles in the developmental control of hematopoiesis, pigmentation, and germ cells. mRNAs that encode both the factor and its receptor have been found to undergo differential splicing in the mouse as well as in humans. As a result of the splicing, isoforms of the protein encoding MGF are expressed that may be sensitive or resistant to cleavage by a protease. This splicing may regulate whether a soluble or membrane bound form of MGF is produced. Both soluble and membrane bound forms of MGF have been shown to be biologically active in vitro, although they may function differently in vivo. Alternate splicing of c-kit mRNA also takes place; several isoforms of the c-kit proto-oncogene have been found that differ by the addition of four amino acids in the extracellular doMayn. These isoforms may differentially modulate the tyrosine kinase activity of c-kit in the absence and/or presence of ligand. The control of mRNA splicing that regulates the production of MGF and c-kit isoforms is likely to play an important role in the biological regulation of multiple cell lineages.