A new intracellular serine protease inhibitor expressed in the rat pituitary gland complexes with granzyme B

• Published in: FEBS letters 1998-12, Vol.440 (3), p.361-364
• Main Authors: Hill, Rena M, Morresey, Kate S, Coates, Leigh C, Mezey, Eva, Fell, Brennan, Bratt, Tomas, Trapani, Joseph A, Birch, Nigel P
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; DNA, Complementary - analysis; Granzyme B; Granzymes; Humans; Inhibitor; Molecular Sequence Data; Neuropeptides; Neuroserpin; Ovalbumin - metabolism; PAI-2, plasminogen activator inhibitor-2; PI-6, protease inhibitor-6; PI-8, protease inhibitor-8; PI-9, protease inhibitor-9; Pituitary; Pituitary Gland - metabolism; raPIT5a, rat pituitary serine protease inhibitor 5a; Rats; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Serine Endopeptidases - metabolism; Serine protease; Serine Proteinase Inhibitors - biosynthesis; Serine Proteinase Inhibitors - genetics; Serpin; Serpin, serine protease inhibitor; Serpins - biosynthesis; Serpins - genetics; SPI6, CrmA, cytokine response modifier A; t-PA, tissue-type plasminogen activator; u-PA, urokinase-type plasminogen activator
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01475-6

We have cloned a novel serpin (raPIT5a) from a rat pituitary cDNA library which is structurally related to members of the ovalbumin subfamily of serine protease inhibitors. This new cDNA encodes a 374-amino acid protein, designated raPIT5a. raPIT5a was expressed in specific cells in the intermediate and anterior lobes of the pituitary. Recombinant raPIT5a was not secreted suggesting raPIT5a functions to inhibit intracellular proteases. Recombinant raPIT5a formed an SDS-stable complex with human granzyme B, a serine protease which induces apoptosis by activating members of the caspase enzyme family. These data suggest raPIT5a may have a role in regulating granzyme B or related enzymes and apoptosis in the pituitary gland.