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… 
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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.

Hepatocyte growth factor activator inhibitor-2 prevents shedding of matriptase.

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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