Ortho-Mcneil Pharmaceutical Corp.

Patricia Andrade-Grodon

Andrew Lawrence Darrow

Jenson Qi

Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed protease T. The deduced amino acid sequence encodes a prepro form of 290 amino acids, and its alignment with other well-characterized serine proteases indicates that it is a member of the S1 serine protease family. We have found that the protease T mRNA is expressed in stomach, testis, retina, fibroblasts, spinal cord, and several regions of the brain. Protease T mRNA is also found in leukocytes and in the Jurkat (ATCC TIB-152) T cell line. Thus, this protease is potentially involved in gastric, testicular, retinal, dematological, neurological/neurodegenerative and/or immunological disorders. The protease T gene maps to human chromosome 16p13.3 which is near the tryptase locus. Enzymatically active protease T, we have generated, is amenable to further biochemical analyses for the identification of physiological substrates and specific modulators.

DNA encoding the human serine protease T

Cleaning compositions containing human serine protease T

Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed protease C-E. The deduced amino acid sequence, and it alignment with other well-characterized serine proteases indicates that it is a member of the S1 serine protease family. We have found that the protease C-E mRNA is expressed in pancreas, placenta, prostate, small intestine, stomach, spleen, fibroblasts and epidermis, as well as in certain regions of the brain i.e., cerebellum, cerebral cortex, pituitary and hippocampus. Enzymatically active protease C-E, as produced using the methodologies described herein, is amenable to further biochemical analyses for the identification of physiological substrates and specific modulators.

Assays for compounds modulating human serine protease C-E

Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed protease T. The deduced amino acid sequence encodes a prepro form of 290 amino acids, and its alignment with other well-characterized serine proteases indicates that it is a member of the S1 serine protease family. We have found that the protease T mRNA is expressed in stomach, testis, retina, fibroblasts, spinal cord, and several regions of the brain. Protease T MRNA is also found in leukocytes and in the Jurkat (ATCC TIB-152) T cell line. Thus, this protease is potentially involved in gastric, testicular, retinal, dematological, neurological/neurodegenerative and/or immunological disorders. The protease T gene maps to human chromosome 16p13.3 which is near the tryptase locus. Enzymatically active protease T, we have generated, is amenable to further biochemical analyses for the identification of physiological substrates and specific modulators.

We describe the DNA sequences encoding an expression vector system that will permit, through limited proteolysis, the activation of expressed zymogen precursor of (S1) serine proteases in a highly controlled and reproducible fashion. The processed expressed protein, once activated, is rendered in a form amenable to measuring the catalytic activity. This catalytic activity of the activated form, is often a more accurate representation of the mature S1 protease gene product relative to the unprocessed zymogen precursor. Thus, this series of zymogen activation constructs represents a significant system for the analysis and characterization of serine protease gene products.

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Doylestown, PA, United States of America

Patricia Andrade-Grodon