Role of Intrapancreatic SPINK1/Spink3 Expression in the Development of Pancreatitis.

Frontiers in Physiology
Masaki OhmurayaKen-ichi Yamamura

Abstract

Studies on hereditary pancreatitis have provided evidence in favor of central role for trypsin activity in the disease. Identification of genetic variants of trypsinogen linked the protease to the onset of pancreatitis, and biochemical characterization proposed an enzymatic gain of function as the initiating mechanism. Mutations of serine protease inhibitor Kazal type 1 gene (SPINK1) are shown to be associated with hereditary pancreatitis. We previously reported that Spink3 (a mouse homolog gene of human SPINK1) deficient mice showed excessive autophagy, followed by inappropriate trypsinogen activation in the exocrine pancreas. These data indicate that the role of SPINK1/Spink3 is not only trypsin inhibitor, but also negative regulator of autophagy. On the other hand, recent studies showed that high levels of SPINK1 protein detected in a serum or urine were associated with adverse outcome in various cancer types. It has been suggested that expression of SPINK1 and trypsin is balanced in normal tissue, but this balance could be disrupted during tumor progression. Based on the structural similarity between SPINK1 and epidermal growth factor (EGF), we showed that SPINK1 protein binds and activates EGF receptor, thus acting as a gr...Continue Reading

Citations

Mar 13, 2014·Biochemical and Biophysical Research Communications·Nobuyuki OzakiMasaki Ohmuraya
Aug 27, 2014·Frontiers in Physiology·Atsushi Masamune
Aug 12, 2014·Molecular Medicine·Rui KangDaolin Tang
Jul 31, 2013·Current Opinion in Gastroenterology·Raghuwansh P SahAshok K Saluja
May 31, 2017·EMBO Molecular Medicine·Zine-Eddine KherrafChristophe Arnoult
Feb 14, 2014·Experimental Animals·Kazuya SakataKen-Ichi Yamamura
Aug 1, 2014·The Journal of Biological Chemistry·Raghuwansh P SahAshok K Saluja
Oct 27, 2020·Frontiers in Cell and Developmental Biology·Lucia ZalazarAndreina Cesari
May 1, 2021·International Journal of Molecular Sciences·Tsung-Chieh Lin
Jun 17, 2021·Biology of Reproduction·Wenfeng XiongZhugang Wang

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Methods Mentioned

BETA
transgenic
gene knockout
immunoprecipitation
quartz-crystal microbalance

Software Mentioned

PyMOL
ZDOCK

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