HAI-1 regulates activation and expression of matriptase, a membrane-bound serine protease.

@article{Oberst2005HAI1RA,
  title={HAI-1 regulates activation and expression of matriptase, a membrane-bound serine protease.},
  author={Michael D. Oberst and Li-Yuan L Chen and Ken-ichi Kiyomiya and Cicely A. Williams and Ming-Shyue Lee and Michael D. Johnson and Robert B. Dickson and Chen-Yong Lin},
  journal={American journal of physiology. Cell physiology},
  year={2005},
  volume={289 2},
  pages={
          C462-70
        }
}
Hepatocyte growth factor activator inhibitor-1 (HAI-1) was initially identified as cognate inhibitor of matriptase, a membrane-bound serine protease. Paradoxically, HAI-1 is also required for matriptase activation, a process that requires sphingosine 1-phosphate (S1P)-mediated translocation of the protease to cell-cell junctions in human mammary epithelial cells. In the present study, we further explored how HAI-1 regulates this protease. First, we observed that after S1P treatment HAI-1 was… 

Figures from this paper

Mechanisms for the control of matriptase activity in the absence of sufficient HAI-1.

Cells with insufficient HAI-1 are investigated for the mechanisms through which the activity of matriptase is regulated and data suggest thatMatriptase activity can be rapidly inhibited by HAi-1 and other HAI -1-like protease inhibitors and "locked" in an inactive autoactivation intermediate, all of which places matript enzyme under very tight control.

Purification from human milk of matriptase complexes with secreted serpins: mechanism for inhibition of matriptase other than HAI-1.

Identification of matriptase-serpin inhibitor complexes provides evidence for the first time that the proteolytic activity ofMatriptase, from those cells that express no or low levels of HAI-1, may be controlled by secreted serpins.

Regulation of the Matriptase-Prostasin Cell Surface Proteolytic Cascade by Hepatocyte Growth Factor Activator Inhibitor-1 during Epidermal Differentiation*

The data suggest that, during epidermal differentiation, the matriptase-prostasin proteolytic cascade is tightly regulated by two mechanisms: 1) prostasin activation temporally coupled to matript enzyme autoactivation and 2) HAI-1 rapidly inhibiting not only activeMatriptase but also active prostasin, resulting in an extremely brief window of opportunity for both active matriptases and active prostatin to act on their substrates.

Crystal Structures of Matriptase in Complex with Its Inhibitor Hepatocyte Growth Factor Activator Inhibitor-1*

Crystal structures elucidate the structural basis of inhibition of matriptase by HAI-1 KD1 and find that the binding of KD1 was different from previously predicted binding mode, which provides important structural insights for the future design of small molecular inhibitors.

Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary.

It is suggested that HGF (hepatocyte growth factor) activator inhibitor-1, in addition to its protease inhibitory function, plays a role in transporting matriptase as a matript enzyme-HAI-1 complex from the basolateral plama membrane to the apical plasma membrane, asMatriptase is known to interact with prostasin, located at the apICAL plasma membrane.

Autoactivation of matriptase in vitro: requirement for biomembrane and LDL receptor domain.

It is shown that a burst of matriptase activation and HAI-1-mediated inhibition spontaneously occurred in the insoluble fractions of cell homogenates and that this in vitro activation could be attenuated by a soluble suppressive factor(s) in cytosolic fractions.

Activation of a membrane-bound serine protease matriptase on the cell surface.

The activation of matriptase may occur when the enzyme reaches the cell surface, as found in the lumen of post-Golgi secretory vesicles.

Aberrant regulation favours matriptase proteolysis in neoplastic B-cells that co-express HAI-2

It is shown that HAI-2 is commonly co-expressed in matriptase-expressing neoplastic B-cells, and the survey suggests that matript enzyme proteolysis might aberrantly remain high in neoplasia regardless of the levels of HAi-2.

Differential Subcellular Localization Renders HAI-2 a Matriptase Inhibitor in Breast Cancer Cells but Not in Mammary Epithelial Cells

It is shown that matriptase inhibition by HAI-2 depends on the subcellular localizations of HAi-2, and is observed in breast cancer cells but not in mammary epithelial cells, and requires the translocation of HA i-2 to the cell surface.
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References

SHOWING 1-10 OF 30 REFERENCES

Regulation of the activity of matriptase on epithelial cell surfaces by a blood-derived factor.

It is demonstrated that matriptase is transiently activated on 184A1N4 human mammary epithelial cell surfaces following their exposure to serum, which is highly conserved across reptilian, avian, and mammalian species.

Simultaneous activation and hepatocyte growth factor activator inhibitor 1-mediated inhibition of matriptase induced at activation foci in human mammary epithelial cells.

The close temporospatial coupling of matriptase activation with its inhibition suggests that the proteolytic activity of this enzyme must be well controlled and thatThe proteolysis ofMatriptase substrates may be tightly regulated by this mechanism.

Matriptase and HAI-1 are expressed by normal and malignant epithelial cells in vitro and in vivo.

Purification and Characterization of a Complex Containing Matriptase and a Kunitz-type Serine Protease Inhibitor from Human Milk*

The results suggest that the milk-derived matriptase complexes are likely to be produced by the epithelial components of the lactating mammary gland in vivo and that the activity and function of matript enzyme may be differentially regulated by its cognate inhibitor, comparing breast cancer with the lactates gland.

Activation of Hepatocyte Growth Factor and Urokinase/Plasminogen Activator by Matriptase, an Epithelial Membrane Serine Protease*

It is suggested that matriptase could act as an epithelial, upstream membrane activator to recruit and activate stromal-derived downstream effectors important for extracellular matrix degradation and epithelial migration, two major events of tissue remodeling, cancer invasion, and metastasis.

Deregulated activation of matriptase in breast cancer cells

Results show that in non-transformed cells, S1P induces a rearrangement of the actin cytoskeleton and stimulates proteolytic activity on cell surfaces, and it is demonstrated that treatment of T-47D cells with epidermal growth factor, which promotes cell ruffle, stimulates increased accumulation of activated matriptase at the sites of membrane ruffling, suggesting a possible functional role at these sites.

The Activation of Matriptase Requires Its Noncatalytic Domains, Serine Protease Domain, and Its Cognate Inhibitor*

It is shown that activation of matriptase requires proteolytic processing at Gly-149 in the SEA domain of the protease, glycosylation of the first CUB domain and the serine protease domain, and intact low density lipoprotein receptor class A domains, and its cognate inhibitor.

Inhibition of Tumor Invasion by Genomic Down-regulation of Matriptase through Suppression of Activation of Receptor-bound Pro-urokinase*

The data identify a novel role for matriptase for activation of receptor-bound uPA and contributes to the invasiveness of HRA human ovarian cancer cells in vitro and tumor behavior in nude mice.

Tissue Expression, Protease Specificity, and Kunitz Domain Functions of Hepatocyte Growth Factor Activator Inhibitor-1B (HAI-1B), a New Splice Variant of HAI-1*

The functions of the KD1 and KD2 domains in sHAI-1B were investigated using P1 residue-directed mutagenesis to show that inhibition of HGFA, matriptase, trypsin, and plasmin was due to KD2 and not KD2.

Assembly of adherens junctions is required for sphingosine 1-phosphate-induced matriptase accumulation and activation at mammary epithelial cell-cell contacts.

It is indicated that actin cytoskeletal rearrangement is necessary but not sufficient for S1P-induced activation of matriptase at cell-cell contacts, and the coupling ofMatriptase activation to adherens junction assembly and act in cytoskeleton rearrangements may serve to ensure tight control ofmatriptase activity, restricted to cell- cell junctions of mammary epithelial cells.