| SPINK1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | SPINK1, PCTT, PSTI, Spink3, TATI, TCP, serine peptidase inhibitor, Kazal type 1, serine peptidase inhibitor Kazal type 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 167790; MGI: 106202; GeneCards: SPINK1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Pancreatic secretory trypsin inhibitor (PSTI) also known as serine protease inhibitor Kazal-type 1 (SPINK1) or tumor-associated trypsin inhibitor (TATI) is a protein that in humans is encoded by the SPINK1 gene.[5] In the context of rat biology, it is also sometimes called monitor peptide.[6]
Structure
Rat monitor peptide is composed of 61 amino acids (compared to 56 in humans) with a molecular weight of approximately 6500 daltons and is basic (PI = 9.0), acid stable, and heat resistant.[7] It is only found in the zymogen granules of pancreatic acinar cells.[7]
Function
SPINK functions as a competitive inhibitor of trypsin, which is a protease that can activate other proteases.[8] It has been shown to prevent premature activation of pancreatic enzymes.[8]
In rats
In addition to its role as a trypsin inhibitor, in rats it has also been found to stimulate the release of CCK from the enteroendocrine cells of the small intestine, and it has been called "monitor peptide" in this context.[9][10][11] CCK then acts on the gallbladder to release bile and on the pancreas to release digestive enzymes, which help to further break down the food. This coordinated response helps to ensure efficient digestion and absorption of nutrients.
Monitor peptide binds to intestinal epithelial cells and induces CCK-release, which enhances pancreatic secretion in the presence of nutritional protein in the duodenum.[12] When all nutritional protein is digested, monitor peptide is bound by trypsin and subsequently degraded, resulting in decreasing CCK-release and a reduction of pancreatic secretion.[12]
Similar to CCK-releasing peptide (CCK-RP, homologous to DBI), it is trypsin sensitive and stimulates CCK release.[7] It is possible that it also stimulates the growth of intestinal epithelial cells.[13]
Clinical significance
Mutations in SPINK1 has been associated with hereditary pancreatitis and tropical pancreatitis. Trypsinogen is normally created and stored an inactive zymogen of trypsin in the pancreas, but occasionally will autoactivate itself. PSTI serves to cleave prematurely activated trypsin to prevent the enzyme from causing cellular damage to the organ. Without the function of PSTI, the pancreas is subject to repeated episodes of damage.[14]
It has also been associated with prostate cancer.[15]
History
Monitor peptide was discovered in 1984 when it was purified from rat bile-pancreatic juice and the peptide sequence was elucidated.[9][16]
See also
References
- GRCh38: Ensembl release 89: ENSG00000164266 – Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000024503 – Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: SPINK1 serine peptidase inhibitor, Kazal type 1".
- "P09655 · ISK1_RAT". UniProt. UniProt consortium. Retrieved 2026-09-23.
- Thompson J (2012). Gastrointestinal Endocrinology: Receptors and Post-Receptor Mechanisms. Elsevier Science. p. 300. ISBN 978-0-323-14642-5. Retrieved 2023-03-25.
- Graf R, Klauser S, Fukuoka SI, Schiesser M, Bimmler D (2003). "The bifunctional rat pancreatic secretory trypsin inhibitor/monitor peptide provides protection against premature activation of pancreatic juice". Pancreatology. 3 (3). Elsevier BV: 195–206. doi:10.1159/000070729. PMID 12771515.
- Miyasaka K, Nakamura R, Funakoshi A, Kitani K (1989). "Stimulatory effect of monitor peptide and human pancreatic secretory trypsin inhibitor on pancreatic secretion and cholecystokinin release in conscious rats". Pancreas. 4 (2). Ovid Technologies (Wolters Kluwer Health): 139–144. doi:10.1097/00006676-198904000-00001. PMID 2755938.
- Vella A (2015). "Gastrointestinal Hormone and Gut Endocrine Tumors". In Kronenberg HM, Polonsky KA, Larsen PR, Melme S (eds.). Williams Textbook of Endocrinology. Internal Medicine. Elsevier Health Sciences. p. 1714. ISBN 978-0-323-29738-7. Retrieved 2023-03-25.
- Yamanishi R, Kotera J, Fushiki T, Soneda T, Iwanaga T, Sugimoto E (January 1993). "Characteristic and Localization of the Monitor Peptide Receptor". Bioscience, Biotechnology, and Biochemistry. 57 (7). Informa UK Limited: 1153–1156. doi:10.1271/bbb.57.1153. PMID 27280999.
- Graf R, Bimmler D (June 2006). "Biochemistry and biology of SPINK-PSTI and monitor peptide". Endocrinology and Metabolism Clinics of North America. 35 (2). Elsevier BV: 333–43, ix. doi:10.1016/j.ecl.2006.02.005. PMID 16632096.
- Fukuda M, Fujiyama Y, Sasaki M, Andoh A, Bamba T, Fushiki T (1998). "Monitor peptide (rat pancreatic secretory trypsin inhibitor) directly stimulates the proliferation of the nontransformed intestinal epithelial cell line, IEC-6". Digestion. 59 (4). S. Karger AG: 326–330. doi:10.1159/000007510. PMID 9693203.
- Schneider A. "SPINK1 - serine peptidase inhibitor, Kazal type 1". Wikigenes.
- Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, et al. (June 2008). "The role of SPINK1 in ETS rearrangement-negative prostate cancers". Cancer Cell. 13 (6): 519–528. doi:10.1016/j.ccr.2008.04.016. PMC 2732022. PMID 18538735.
- Fushiki T, Fukuoka S, Iwai K (January 1984). "Stimulatory effect of an endogenous peptide in rat pancreatic juice on pancreatic enzyme secretion in the presence of atropine: evidence for different mode of action of stimulation from exogenous trypsin inhibitors". Biochemical and Biophysical Research Communications. 118 (2). Elsevier BV: 532–537. doi:10.1016/0006-291x(84)91335-4. PMID 6704094.
Further reading
- Marchbank T, Freeman TC, Playford RJ (1998). "Human pancreatic secretory trypsin inhibitor. Distribution, actions and possible role in mucosal integrity and repair". Digestion. 59 (3): 167–174. doi:10.1159/000007485. PMID 9643675.
- Pfützer RH, Whitcomb DC (2002). "SPINK1 mutations are associated with multiple phenotypes". Pancreatology. 1 (5): 457–460. doi:10.1159/000055847. PMID 12120224. S2CID 8123648.
- Schneider A (March 2005). "Serine protease inhibitor kazal type 1 mutations and pancreatitis". Clinics in Laboratory Medicine. 25 (1): 61–78. doi:10.1016/j.cll.2004.12.005. PMID 15749232.
- Cohn JA, Mitchell RM, Jowell PS (March 2005). "The impact of cystic fibrosis and PSTI/SPINK1 gene mutations on susceptibility to chronic pancreatitis". Clinics in Laboratory Medicine. 25 (1): 79–100. doi:10.1016/j.cll.2004.12.007. PMID 15749233.
- Kandula L, Whitcomb DC, Lowe ME (June 2006). "Genetic issues in pediatric pancreatitis". Current Gastroenterology Reports. 8 (3): 248–253. doi:10.1007/s11894-006-0083-8. PMID 16764792. S2CID 23606613.
- Bartelt DC, Shapanka R, Greene LJ (February 1977). "The primary structure of the human pancreatic secretory trypsin inhibitor. Amino acid sequence of the reduced S-aminoethylated protein". Archives of Biochemistry and Biophysics. 179 (1): 189–199. doi:10.1016/0003-9861(77)90103-5. PMID 843082.
- Hecht HJ, Szardenings M, Collins J, Schomburg D (June 1992). "Three-dimensional structure of a recombinant variant of human pancreatic secretory trypsin inhibitor (Kazal type)". Journal of Molecular Biology. 225 (4): 1095–1103. doi:10.1016/0022-2836(92)90107-U. PMID 1613792.
- Hecht HJ, Szardenings M, Collins J, Schomburg D (August 1991). "Three-dimensional structure of the complexes between bovine chymotrypsinogen A and two recombinant variants of human pancreatic secretory trypsin inhibitor (Kazal-type)". Journal of Molecular Biology. 220 (3): 711–722. doi:10.1016/0022-2836(91)90112-J. PMID 1870127.
- Freeman TC, Davies R, Calam J (December 1990). "Interactions of pancreatic secretory trypsin inhibitor in small intestinal juice: its hydrolysis and protection by intraluminal factors". Clinica Chimica Acta; International Journal of Clinical Chemistry. 195 (1–2): 27–39. doi:10.1016/0009-8981(90)90191-T. PMID 2093478.
- Kido H, Yokogoshi Y, Katunuma N (March 1990). "A low-molecular-mass Kazal-type protease inhibitor isolated from rat hepatocytes is identical to rat pancreatic secretory trypsin inhibitor II. Purification and amino acid sequence". European Journal of Biochemistry. 188 (3): 501–506. doi:10.1111/j.1432-1033.1990.tb15428.x. PMID 2110056.
- Tomita N, Horii A, Yamamoto T, Ogawa M, Mori T, Matsubara K (December 1987). "Expression of pancreatic secretory trypsin inhibitor gene in neoplastic tissues". FEBS Letters. 225 (1–2): 113–119. doi:10.1016/0014-5793(87)81141-9. PMID 2961612. S2CID 20663654.
- Horii A, Kobayashi T, Tomita N, Yamamoto T, Fukushige S, Murotsu T, et al. (December 1987). "Primary structure of human pancreatic secretory trypsin inhibitor (PSTI) gene". Biochemical and Biophysical Research Communications. 149 (2): 635–641. doi:10.1016/0006-291X(87)90415-3. PMID 3501289.
- Yamamoto T, Nakamura Y, Nishide J, Emi M, Ogawa M, Mori T, et al. (October 1985). "Molecular cloning and nucleotide sequence of human pancreatic secretory trypsin inhibitor (PSTI) cDNA". Biochemical and Biophysical Research Communications. 132 (2): 605–612. doi:10.1016/0006-291X(85)91176-3. PMID 3877508.
- Huhtala ML, Pesonen K, Kalkkinen N, Stenman UH (November 1982). "Purification and characterization of a tumor-associated trypsin inhibitor from the urine of a patient with ovarian cancer". The Journal of Biological Chemistry. 257 (22): 13713–13716. doi:10.1016/S0021-9258(18)33505-1. PMID 7142173.
- Klaus W, Schomburg D (February 1993). "Solution structure of a variant of human pancreatic secretory trypsin inhibitor determined by nuclear magnetic resonance spectroscopy". Journal of Molecular Biology. 229 (3): 695–706. doi:10.1006/jmbi.1993.1073. PMID 8433367.
- Chen JM, Mercier B, Audrezet MP, Ferec C (January 2000). "Mutational analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene in hereditary and sporadic chronic pancreatitis". Journal of Medical Genetics. 37 (1): 67–69. doi:10.1136/jmg.37.1.67. PMC 1734438. PMID 10691414.
- Witt H, Luck W, Hennies HC, Classen M, Kage A, Lass U, et al. (June 2000). "Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis". Nature Genetics. 25 (2): 213–216. doi:10.1038/76088. PMID 10835640. S2CID 23661289.
- Pfützer RH, Barmada MM, Brunskill AP, Finch R, Hart PS, Neoptolemos J, et al. (September 2000). "SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis". Gastroenterology. 119 (3): 615–623. doi:10.1053/gast.2000.18017. PMID 10982753.
- Kaneko K, Nagasaki Y, Furukawa T, Mizutamari H, Sato A, Masamune A, et al. (2001). "Analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene mutations in Japanese patients with chronic pancreatitis". Journal of Human Genetics. 46 (5): 293–297. doi:10.1007/s100380170082. PMID 11355022.