Identification and cloning of ELF-1, a developmentally expressed ligand for the Mek4 and Sek receptor tyrosine kinases.
Mek4 and Sek are tyrosine kinases with expression patterns in the mouse embryo that suggest important functions in early development. However, like all Eph family kinases, both were identified as orphan receptors without known ligands. We show that Mek4 and Sek soluble receptor-alkaline phosphatase fusion proteins can be used in a procedure termed RAP in situ to identify regions of ligand expression in the mouse embryo. Based on this spatial information, a cDNA expression library was prepared, and was screened with the fusion proteins to identify Eph ligand family-1 (ELF-1). In cell lines and embryos, ELF-1 is membrane bound by a phosphatidylinositol tail, a feature that may account for unique biological functions. Its sequence is homologous with B61, a ligand for the Eck kinase, defining a family of related ligands. The expression domains of ELF-1, Mek4 and Sek indicate potential roles in embryonic patterning.
Cheng
H J
HJ
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
Flanagan
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000737:chemistry; D005314:Embryonic and Fetal Development; D036383:Ephrin-A2; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D008024:Ligands; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008636:Mesencephalon / Q000196:embryology; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036122:Receptor, EphA4; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012249:Rhombencephalon / Q000196:embryology; D017386:Sequence Homology, Amino Acid
D036383:Ephrin-A2; D005326:Fetal Proteins; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012313:RNA; D020794:Receptor Protein-Tyrosine Kinases; D036122:Receptor, EphA4