A new ephrin-A1 isoform (ephrin-A1b) with altered receptor binding properties abrogates the cleavage of ephrin-A1a.
Ephrins are ligands for the Eph receptor tyrosine kinases, which play important roles in patterning nervous and vascular systems. Ephrin-A1 is a glycosylphosphatidylinositol-anchored ligand that binds to the EphA receptor tyrosine kinases. In the present study, we have identified a new ephrin-A1 isoform, denoted ephrin-A1b (ephrin-A1 isoform b). Compared with the originally described ephrin-A1 sequence, ephrin-A1a [Holzman, Marks and Dixit (1990) Mol. Cell. Biol. 10, 5830-5838], ephrin-A1b lacks a segment of 22 amino acids (residues 131-152). At the transcript level, exon 3 is spliced out in the transcript encoding ephrin-A1b. Transfection of HEK-293T cells (human embryonic kidney 293 cells) with an ephrin-A1b-expressing plasmid resulted in a significant expression of the protein on the cell surface. However, soluble EphA2 receptor (EphA2-Fc) bound weakly to ephrin-A1b-expressing transfectants, but bound strongly to ephrin-A1a-expressing transfectants. Ephrins have been shown to undergo regulated cleavage after interaction with their receptors. This process is inhibited by co-expression of ephrin-A1a and ephrin-A1b, indicating that ephrin-A1b influences the cleavage process. Taken together, these findings indicate that this newly described isoform may regulate the function of its ephrin-A1a counterpart.
Finne
Eivind F
EF
Department of Immunology, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway.
Munthe
Else
E
Aasheim
Hans-Christian
HC
D000595:Amino Acid Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D036382:Ephrin-A1 / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D005091:Exons / Q000235:genetics; D005796:Genes; D006801:Humans; D007668:Kidney; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D014066:Palatine Tonsil; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D012326:RNA Splicing; D036081:Receptors, Eph Family / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection
D018076:DNA, Complementary; D036382:Ephrin-A1; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D036081:Receptors, Eph Family