PATE gene clusters code for multiple, secreted TFP/Ly-6/uPAR proteins that are expressed in reproductive and neuron-rich tissues and possess neuromodulatory activity. Levitin, F; Weiss, M; Hahn, Y; Stern, O; Papke, RL; Matusik, R; Nandana, SR; Ziv, R; Pichinuk, E; Salame, S; Bera, T; Vincent, J; Lee, B; Pastan, I; Wreschner, DH The Journal of biological chemistry
283
16928-39
2008
概要を表示する
We report here syntenic loci in humans and mice incorporating gene clusters coding for secreted proteins each comprising 10 cysteine residues. These conform to three-fingered protein/Ly-6/urokinase-type plasminogen activator receptor (uPAR) domains that shape three-fingered proteins (TFPs). The founding gene is PATE, expressed primarily in prostate and less in testis. We have identified additional human PATE-like genes (PATE-M, PATE-DJ, and PATE-B) that co-localize with the PATE locus, code for novel secreted PATE-like proteins, and show selective expression in prostate and/or testis. Anti-PATE-B-specific antibodies demonstrated the presence of PATE-B in the region of the sperm acrosome and at high levels on malignant prostatic epithelial cells. The syntenic mouse Pate-like locus encompasses 14 active genes coding for secreted proteins, which are all, except for Pate-P and Pate-Q, expressed primarily in prostate and/or testis. Pate-P and Pate-Q are expressed solely in placental tissue. Castration up-regulates prostate expression of mouse Pate-B and Pate-E, whereas testosterone ablates this induced expression. The sequence similarity between TFP/Ly-6/uPAR proteins that modulate activity of nicotinic acetylcholine receptors and the PATE (Pate)-like proteins stimulated us to see whether these proteins possess analogous activity. Pharmacological studies showed significant modulation of the nicotinic acetylcholines by the PATE-B, Pate-C, and Pate-P proteins. In concert with these findings, certain PATE (Pate)-like genes were extensively expressed in neuron-rich tissues. Taken together, our findings indicate that in addition to participation of the PATE (Pate)-like genes in functions related to fertility and reproduction, some of them likely act as important modulators of neural transmission. | 18387948
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PATE, a gene expressed in prostate cancer, normal prostate, and testis, identified by a functional genomic approach. Bera, TK; Maitra, R; Iavarone, C; Salvatore, G; Kumar, V; Vincent, JJ; Sathyanarayana, BK; Duray, P; Lee, BK; Pastan, I Proceedings of the National Academy of Sciences of the United States of America
99
3058-63
2002
概要を表示する
To identify target antigens for prostate cancer therapy, we have combined computer-based screening of the human expressed sequence tag database and experimental expression analysis to identify genes that are expressed in normal prostate and prostate cancer but not in essential human tissues. Using this approach, we identified a gene that is expressed specifically in prostate cancer, normal prostate, and testis. The gene has a 1.5-kb transcript that encodes a protein of 14 kDa. We named this gene PATE (expressed in prostate and testis). In situ hybridization shows that PATE mRNA is expressed in the epithelial cells of prostate cancers and in normal prostate. Transfection of the PATE cDNA with a Myc epitope tag into NIH 3T3 cells and subsequent cell fractionation analysis shows that the PATE protein is localized in the membrane fraction of the cell. Analysis of the amino acid sequence of PATE shows that it has structural similarities to a group of proteins known as three-finger toxins, which includes the extracellular domain of the type beta transforming growth factor receptor. Restricted expression of PATE makes it a potential candidate for the immunotherapy of prostate cancer. | 11880645
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