Heterogeneous modifications of the 114/A10 protein of interleukin-3-dependent cells are concentrated in a highly repetitive amino-terminal domain.
The protein 114/A10 is expressed in structurally heterogeneous forms on the surfaces of all murine hemopoietic cells that are responsive to the growth factor interleukin-3, including multipotent progenitors. Despite their structural diversity, all forms of 114/A10 appear to be expressed from a single gene that encodes a peptide with a potential transmembrane segment, three sequences with homology to epidermal growth factor, and an N-terminal domain consisting of eight perfect or near perfect tandem repeats of a 27-amino acid peptide that has a very high content of serine and threonine. Constructed cDNAs that encode deleted or hybrid forms of the 114/A10 protein have been expressed on COS cells in order to localize sites of post-translational modification. The results demonstrate that the structural diversity of 114/A10 is confined to its N-terminal repeat domain and probably arises through extensive O-linked glycosylation within each of the repeats in that domain. The highly modified N terminus of 114/A10 projects from the outer surface of the cell and could serve as a ligand for lectin-like proteins or could modulate the activities of the adjacent epidermal growth factor-like domains of 114/A10.
Kay
R
R
Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, Canada.
Dougherty
G J
GJ
Humphries
R K
RK
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002872:Chromosome Deletion; D004247:DNA / Q000235:genetics; D004815:Epidermal Growth Factor; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology*; D008961:Models, Structural; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011487:Protein Conformation; D014162:Transfection
D000954:Antigens, Surface; D007377:Interleukin-3; C063487:Ly64 protein, mouse; D004815:Epidermal Growth Factor; D004247:DNA