Disease relevance of St14

• In addition, soluble forms of matriptase were isolated from human breast milk and breast cancer cell-conditioned medium [1].
• This aberrant skin development seriously compromised both inward and outward epidermal barrier function, leading to the rapid and fatal dehydration of Matriptase/MT-SP1-deficient pups [2].
• RESULTS: Matriptase mRNA level was lower in carcinomas compared to normal tissue from healthy individuals (p < 0.01) [3].
• In accordance with this, the matriptase mRNA level was also lower in adenomas/carcinomas combined as compared to their adjacent normal tissue (p < 0.01) [3].
• METHODS: Using quantitative RT-PCR, we have determined the mRNA levels for matriptase and HAI-1 in colorectal cancer tissue (n = 9), severe dysplasia (n = 15), mild/moderate dysplasia (n = 21) and in normal tissue from the same individuals [3].

High impact information on St14

• Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1 [4].
• We show that epidermal deficiency of the transmembrane serine protease Matriptase/MT-SP1 perturbs lipid matrix formation, cornified envelope morphogenesis, and stratum corneum desquamation [4].
• Autosomal Recessive Ichthyosis with Hypotrichosis Caused by a Mutation in ST14, Encoding Type II Transmembrane Serine Protease Matriptase [5].
• We screened the ST14 gene, which encodes matriptase, since transplantation of skin from matriptase(-/-)-knockout mice onto adult athymic nude mice has been shown elsewhere to result in an ichthyosislike phenotype associated with almost complete absence of erupted pelage hairs [5].
• Recent gene ablation studies in mice have shown that matriptase, a type II transmembrane serine protease, and prostasin, a glycosylphosphatidylinositol-anchored membrane serine protease, are both required for processing of the epidermis-specific polyprotein, profilaggrin, stratum corneum formation, and acquisition of epidermal barrier function [6].

Biological context of St14

• This gene, Prss14 (protease, serine, 14), was mapped to mouse chromosome 9 and is closely linked to the Fli1 (Friend leukemia integration 1) gene [7].
• Furthermore, Matriptase/MT-SP1-deficiency resulted in dramatically increased thymocyte apoptosis, and depletion of thymocytes [2].
• Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis [2].
• Post-transcriptional epithin gene silencing by RNA interference (RNAi) resulted in the blockade of 8-cell in vitro-stage embryo compaction and subsequent embryonic deaths after several rounds of cell division [8].
• These data demonstrate that in vivo generated LCM virus-induced cytolytic T lymphocytes develop cytoplasmic storage granules containing MTSP-1 and suggest that the mechanism of granule exocytosis is operative in vivo; possibly MTSP-1 is one effector molecule participating in the Ly-2+(CD8+) T lymphocyte-mediated control of virus infection [9].

Anatomical context of St14

• Cloning and chromosomal mapping of a gene isolated from thymic stromal cells encoding a new mouse type II membrane serine protease, epithin, containing four LDL receptor modules and two CUB domains [7].
• Using somatic cell hybrids, we have obtained data which place probes DX13 (used to detect locus DXS15) and St14 (used to detect DXS52) distal to F8C, within band Xq28 [10].
• The data identify keratinocyte Matriptase/MT-SP1 as an essential component of the profilaggrin-processing pathway and a key regulator of terminal epidermal differentiation [4].
• In addition, we have identified the actin-binding protein, filamin, as the linker between epithin and the actin cytoskeleton [11].
• This study demonstrates that Matriptase/MT-SP1 has pleiotropic functions in the development of the epidermis, hair follicles, and cellular immune system [2].

Associations of St14 with chemical compounds

• We also show that the release of epithin does not require its own activity and is blocked by a metalloprotease inhibitor, GM6001 [11].
• Furthermore, it was shown that purified MTSP-1 is able to release from ECM high-molecular weight proteoglycans and that this process is inhibitable by PFR-CK but not by heparin [12].
• More than 50% of Ly-2+(CD8+) cells but only low numbers of Ly-2-(CD8-) cells, previously enriched by flow cytofluorometry, contained large amounts of cytoplasmic granules which stained both with MTSP-1-specific mAb and the esterase substrate N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester [9].
• On the other hand, interaction of MTSP-1 with sulfated glycosaminoglycans, i.e., heparin and chondroitin sulfate, led to increased enzymatic activity and an altered fine specificity of MTSP-1 for peptide substrates [13].

Regulatory relationships of St14

• Here we show, that MTSP-1 was effectively inhibited by vascular and extravascular serpins such as antithrombin III and Cl-esterase inhibitor, as well as by aprotinin and alpha 2-macroglobulin [13].

Other interactions of St14

• Expression of epithin in mouse preimplantation development: its functional role in compaction [8].
• Constitutive mouse T cell-specific proteinase-1 (MTSP-1) activity, constitutive expression of MTSP-1 RNA, increased by Ag challenge, and Ag-inducible perforin RNA expression were observed [14].
• On the other hand, MTSP-2 hydrolyzed Boc-Phe-Ser-Arg-MCA most rapidly, with a specific activity 15 times higher than that of MTSP-1 [15].

Analytical, diagnostic and therapeutic context of St14

• Using site-directed mutagenesis experiments, we identified Gly(149) of the GSVIA sequence in epithin as required for the processing and release of the protein [1].
• RT-PCR analysis showed that epithin mRNAs were detectable during the cleavage stages from a 1-cell zygote to the blastocyst [8].

References