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PMID:10632593
| Citation |
Fricker, LD, McKinzie, AA, Sun, J, Curran, E, Qian, Y, Yan, L, Patterson, SD, Courchesne, PL, Richards, B, Levin, N, Mzhavia, N, Devi, LA and Douglass, J (2000) Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. J. Neurosci. 20:639-48 |
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| Abstract |
Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, the mRNA is broadly distributed among neurons. When expressed in AtT-20 cells, proSAAS is secreted via the regulated pathway and is also processed at paired-basic cleavage sites into smaller peptides. Overexpression of proSAAS in the AtT-20 cells substantially reduces the rate of processing of the endogenous prohormone proopiomelanocortin. Purified proSAAS inhibits prohormone convertase 1 activity with an IC(50) of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1. |
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| Keywords |
Adrenal Glands/metabolism; Amino Acid Sequence; Animals; Base Sequence; Brain/metabolism; Carboxypeptidase H; Carboxypeptidases/deficiency; Carboxypeptidases/genetics; Carboxypeptidases/metabolism; Cell Line; Humans; Kinetics; Mice; Mice, Mutant Strains; Molecular Sequence Data; Neurons/metabolism; Neuropeptides/biosynthesis; Neuropeptides/chemistry; Neuropeptides/genetics; Neuropeptides/metabolism; Organ Specificity; Pancreas/metabolism; Pituitary Gland/metabolism; Pro-Opiomelanocortin/genetics; Pro-Opiomelanocortin/metabolism; Protein Precursors/chemistry; Protein Precursors/genetics; Protein Precursors/metabolism; Protein Processing, Post-Translational; RNA, Messenger/genetics; Rats; Recombinant Proteins/metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Transfection |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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See also
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