3.4.21.B6: prostasin

spatial and temporal co-expression of matriptase and prostasin

731623

malfunction

loss of prostasin expression in the transitional cell carcinoma cell lines is correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation and may have functional implications in tumor invasion and resistance to chemotherapy

707872

malfunction

prostasin silencing in BPH-1 cells is associated with up-regulation of iNOS, ICAM-1, interleukin-6, and interleukin-8, and down-regulation of cyclin D1, as well as reduced proliferation and invasion

710459

malfunction

liver-specific PRSS8 enzyme knockout mice develop insulin resistance associated with the increase in hepatic Toll-like receptor 4, the knockout mice show an excessive response to lipopolysacchrides. Restoration of enzyme expression in livers of high-fat diet, knockout, and db/db mice decreases the TLR4 level and ameliorates insulin resistance, phenotypes, overview

732562

malfunction

matriptase and prostasin null mice have identical phenotypes. mice deficient for matriptase phenocopy mice deficient for epidermal prostasin and show impaired corneocyte differentiation, imparied lipid matrix formation, loss of profilaggrin processing and loss of tight junction formation and function. Together, these defects lead to a compromised epidermal barrier and result in fatal dehydration during the neonatal period. The proteolytic processing of prostasin as well as profilaggrin is greatly reduced in matriptase hypomorphic mice

731623

malfunction

Q99L44

prostasin null mice lack barrier formation and display fatal postnatal dehydration. But mice homozygous for a point mutation in the Prss8 gene, which causes the substitution of the active site serine within the catalytic histidine-aspartate-serine triad with alanine and renders prostasin catalytically inactive, develop barrier function and are healthy when followed for up to 20 weeks. Phenotypes, overview

732131

malfunction

Mus musculus C57BL/6N

metabolism

high-fat diet triggers the suppression of the enzyme expression by inducing endoplasmic reticulum stress and increases the Toll-like receptor 4 level in the liver. Serum enzyme levels are correlated to body mass index and homoeostasis model assessment-insulin resistance

metabolism

metabolism

matriptase and not prostasin is the primary effector protease of tight junction assembly in simple columnar epithelia

732088

physiological function

prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells. Prostasin participates in the proteolytic activation of epithelial sodium channel as well as cleavage of epidermal growth factor receptor extracellular domain in human epithelial cells. Prostasin functions as an invasion suppressor in human trophoblast, participating in the invasion-restrictive regulation of trophoblasts to avoid their over-penetration into the uterine wall

708646

physiological function

prostasin is essential for terminal epithelial differentiation, prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor and is an invasion suppressor

707872

physiological function

prostasin regulates human placental trophoblast cell proliferation via modulating the epidermal growth factor receptor-mitogen-activated protein kinase signaling pathway

708673

physiological function

prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells. Prostasin plays a negative regulatory role on protease-activated receptor-2-mediated signaling in prostate epithelial cell

710459

physiological function

prostasin significantly increases both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner

709175

physiological function

prostasin significantly increases both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner. Prostasin has a stimulatory effect on the aldosterone synthesis by adrenal gland through the nonproteolytic action

709175

physiological function

Prostasin catalyzed activation of ENaC induces an open channel conformation associated with sodium influx that results in membrane depolarization. Prostasin together with matriptase comprise a single common proteolytic pathway,that is required for barrier formation. Prostasin is activated through proteolytic cleavage by matriptase, but prostasin is also required for matriptase activation in intestinal epithelial cells to regulate closure of the paracellular pathway

732088

physiological function

Xenopus laevis

Q9ES87

prostasin interacts with the epithelial Na+ channel, the catalytically inactive prostasin facilitates the cleavage of the gamma-subunit by an endogenous protease in Xenopus oocytes, cleavage of the gamma-subunit by furin at the consensus site gammaRKRR143 and subsequent cleavage by a second protease at a distal site strongly activate the channel

731108

physiological function

prostasin is also a regulator of the epidermal sodium channel like matriptase

717902

physiological function

Q99L44

prostasin supports epidermal development and postnatal homeostasis independent of its enzymatic activity

732131

physiological function

the enzyme has the ability to activate epithelial sodium channels and effect the sodium current across the plasma membrane in vitro. In the epidermis, the glycosylphosphatidylinositol anchored membrane serine protease prostasin is activated by matriptase to initiate a proteolytic cascade that is required for the development of the stratum corneum barrier function. Proteolytic activity of the matriptase-prostasin cascade is regulated in the epidermis via inhibition by the Kunitz-type serine protease inhibitor hepatocyte growth factor activator inhibitor-1

731623

physiological function

the serine protease prostasin regulates hepatic insulin sensitivity by modulating Toll-like receptor 4-mediated signalling, the enzyme decreases TLR4 levels by the proteolytic shedding

732562

physiological function

the serine protease prostasin regulates hepatic insulin sensitivity by modulating Toll-like receptor 4-mediated signalling, the enzyme decreases TLR4 levels by the proteolytic shedding

732562

physiological function

HAI-1 but not HAI-2 is the prominent inhibitor for prostasin and matriptase in skin. The limited role for HAI-2 in the inhibition of matriptase and prostasin is the result of its primarily intracellular localization in basal and spinous layer keratinocytes, which probably prevents the HAI-2 from interacting with active prostasin or matriptase

755167

physiological function

knock-in mice expressing catalytically inactive prostasin display normal prenatal and postnatal survival. Catalytically inactive prostasin causes embryonic lethality in mice lacking its cognate inhibitors HAI-1 (SPINT1) or HAI-2 (SPINT2). Proteolytically inactive prostasin, unlike the wild-type protease, is unable to activate matriptase during placentation. All essential functions of prostasin in embryonic and postnatal development are compensated for by loss of HAI-1

753383

physiological function