Prss2

What is PRSS2 protein?

PRSS2 (serine protease 2) gene is a protein coding gene which situated on the long arm of chromosome 7 at locus 7q34. This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. It consists of a signal peptide (residues 1-15), a pro region (residues 16-23), and a proteolytically active mature chain (residues 24-247). The PRSS2 protein is consisted of 247 amino acids and its molecular mass is approximately 26.5 kDa.

What is the function of PRSS2 protein?

PRSS2 is widely present in various tissues and organs of the human body. Its main function is to participate in the protein digestion process of the digestive system. SP2 is able to break proteins down into small peptides and amino acids so that they can be easily absorbed. In addition, SP2 is also involved in cell signaling, tumorigenesis and development, inflammation and other biological processes.

Fig1. Schematic drawing illustrating the effects of asparaginase on pancreatic acinar cells. (Benjamin O Wolthers, 2019)

PRSS2 Related Signaling Pathway

PRSS2 is involved in multiple signaling pathways, including cell proliferation, migration, apoptosis, and inflammation. PRSS2 regulates cell growth and survival by activating signaling pathways such as MAPK, PI3K/AKT, and NF-κB. For example, it can activate the AKT signaling pathway, promoting cell survival and anti-apoptosis. In addition, PRSS2 is also involved in the regulation of inflammatory responses, as it can cut and activate several pro-inflammatory cytokines, such as IL-1β and IL-8.

PRSS2 Related Diseases

PRSS2 has been found to be associated with a variety of diseases, the most prominent of which are pancreatic diseases such as chronic pancreatitis and pancreatic cancer. In addition, PRSS2 has been associated with the development of several other pancreatic diseases, intestinal diseases, and certain tumors such as gastric cancer.

Bioapplications of PRSS2

PRSS2 can be used to screen potential drug candidate molecules and assess their effects on target proteins. In clinical diagnosis, PRSS2 is used as a marker for certain diseases, which can help doctors assess the health status of patients, such as pancreatitis, kidney disease, etc.

Case study 1: Lufei Sui, 2022

The progression of cancer from localized to metastatic disease is the primary cause of morbidity and mortality. The interplay between the tumor and its microenvironment is the key driver in this process of tumor progression. In order for tumors to progress and metastasize they must reprogram the cells that make up the microenvironment to promote tumor growth and suppress endogenous defense systems, such as the immune and inflammatory response. The stimulation of Tsp-1 in the tumor microenvironment (TME) potently inhibits tumor growth and progression. Here, we identify a novel tumor-mediated mechanism that represses the expression of Tsp-1 in the TME via secretion of the serine protease PRSS2. They found that PRSS2 represses Tsp-1, not via its enzymatic activity, but by binding to low-density lipoprotein receptor-related protein 1 (LRP1). These findings describe a hitherto undescribed activity for PRSS2 through binding to LRP1 and represent a potential therapeutic strategy to treat cancer by blocking the PRSS2-mediated repression of Tsp-1.

Fig1. Tsp-1 and actin levels in MRC5 fibroblasts and primary human peripheral blood mononuclear cells (PBMCs) that were untreated (–) or treated with recombinant human PRSS2 ( + ).

Fig2. Dot plot of quantitation of Tsp-1 western blots from all replicates of WI38 that were untreated (–) or treated with PRSS2 (+) in the absence (–) and presence (+) of NSC23766.

Case study 2: T Sorsa, 1997

Increased production of proteinases, such as matrix metalloproteinases (MMPs), is a characteristic feature of malignant tumors. Some human cancers and cell lines derived from them also express trypsinogen, but the function of the extrapancreatic trypsin has remained unclear. In this study they researchers cloned and sequenced trypsinogen-2 cDNA from human COLO 205 colon carcinoma cells and characterized the ability of the enzyme to activate latent human type IV procollagenases (proMMP-2 and proMMP-9). As shown by cloning and N-terminal amino acid sequencing, the amino acid sequence of tumor-associated trypsin-2 is identical to that of pancreatic trypsin-2. They found that both pancreatic trypsin-2 and tumor cell-derived trypsin-2 are efficient activators of proMMP-9 Human trypsin-2 was a more efficient activator than widely used bovine trypsin and converted the 92-kDa proMMP-9 to a single 77-kDa product that was not fragmented further. In contrast, trypsin-2 only partially activated proMMP-2. Trypsin-2 cleaved the Arg99-Lys100 peptide bond of proMMP-2 generating 62-65-kDa MMP-2 species. The ability of human tumor cell-derived trypsin-2 to activate latent MMPs suggests a role for trypsin-2 in initiating the proteinase cascade that mediates tumor invasion and metastasis formation.

Fig3. Comparison of activation of proMMP-9 with human trypsin-2 and bovine trypsin as analyzed by gelatin zymography.

Fig4. Correlation between the increase in specific activity of MMP-9 and the generation of 77-kDa MMP-9 species.

Prss2 has several biochemical functions, for example, calcium ion binding,protein binding,serine-type endopeptidase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by Prss2 itself. We selected most functions Prss2 had, and list some proteins which have the same functions with Prss2. You can find most of the proteins on our site.

Prss2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Prss2 here. Most of them are supplied by our site. Hope this information will be useful for your research of Prss2.