Abstract: |
Human Prostate Specific Membrane Antigen (PSMA), also known as folate hydrolase I (FOLH1), is a 750-amino acid type II membrane glycoprotein, which is primarily expressed in normal human prostate epithelium and is upregulated in prostate cancer, including metastatic disease. We have cloned and sequenced the mouse homolog of PSMA, which we have termed Folh 1, and have found that it is not expressed in the mouse prostate, but primarily in the brain and kidney. We have demonstrated that Folh 1, like its human counterpart, is a glutamate-preferring carboxypeptidase, which has at least two enzymatic activities: (1) N-acetylated α-linked L-amino dipeptidase (NAALADase), an enzyme involved in regulation of excitatory signaling in the brain, and (2) a γ-glutamyl carboxypeptidase (folate hydrolase). The 2,256-nt open reading frame of Folh 1 encodes for a 752-amino acid protein, with 86% identity and 91% similarity to the human PSMA amino acid sequence. Cells transfected with Folh 1 gained both NAALADase and folate hydrolase activities. Examination of tissues for NAALADase activity correlated with the mRNA expression pattern for Folh 1. Fluorescent in situ hybridization (FISH) revealed Folh1 maps to only one locus in the mouse genome, Chromosome 7D 1-2. |
Keywords: |
controlled study; nonhuman; mouse; animals; mice; animal tissue; in situ hybridization, fluorescence; reverse transcription polymerase chain reaction; cell line; enzyme activity; transfection; animalia; prostate cancer; gene expression regulation; molecular cloning; cloning, molecular; prostate specific membrane antigen; fluorescence in situ hybridization; amino acid sequence; molecular sequence data; reverse transcriptase polymerase chain reaction; rna, messenger; nucleotide sequence; organ specificity; base sequence; genome; blotting, northern; complementary dna; glutamate carboxypeptidase ii; antigens, surface; complementary rna; chromosomal localization; sequence analysis, dna; prostate disease; open reading frames; male genital tract cancer; gamma glutamyl hydrolase; male; article; carboxypeptidases
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