Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family.
Cultured pigment epithelial cells of the fetal human retina secrete a protein, pigment epithelium-derived factor (PEDF), that induces a neuronal phenotype in cultured human retinoblastoma cells. Morphological changes include the induction of an extensive neurite meshwork and the establishment of corona-like cellular aggregates surrounding a central lumen. The differentiated cells also show increases in the expression of neuron-specific enolase and the 200-kDa neurofilament subunit. Amino acid and DNA sequence data demonstrate that PEDF belongs to the serine protease inhibitor (serpin) family. The PEDF gene contains a typical signal-peptide sequence, initiator methionine codon, and polyadenylylation signal and matches the size of other members of the serpin superfamily (e.g., alpha 1-antitrypsin). It lacks homology, however, at the putative serpin reactive center. Thus, PEDF could exert a paracrine effect in the embryonic retina, influencing neuronal differentiation by a mechanism that does not involve classic inhibition of serine protease activity.
Steele
F R
FR
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Chader
G J
GJ
Johnson
L V
LV
Tombran-Tink
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004926:Escherichia coli / Q000235:genetics; D005134:Eye Neoplasms; D005136:Eye Proteins / Q000235:genetics* / Q000494:pharmacology*; D005333:Fetus; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009414:Nerve Growth Factors; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009838:Oligodeoxyribonucleotides; D010857:Pigment Epithelium of Eye / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins; D015183:Restriction Mapping; D012175:Retinoblastoma; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D015843:Serpins / Q000235:genetics* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000515:alpha 1-Antitrypsin / Q000235:genetics; D000099174:Pigment Epithelium-Derived Factor
D004247:DNA; D005136:Eye Proteins; D009414:Nerve Growth Factors; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D000515:alpha 1-Antitrypsin; D000099174:Pigment Epithelium-Derived Factor