Matriptase Activation in Breast Cancer Progression
Abstract
In the current research plan, we proposed to study the mechanism for activation of matriptase, a membrane-bound serine protease. Previously, we showed matriptase is activated via transactivation, where the interactions among latent matriptase molecules, HAI-1, and other unidentified proteins are required for the proceeding of activational cleavage. In non-transformed mammary epithelial cells, matriptase activation can be induced by sphingosine 1-phosphate (S1P), a blood-borne bioactive phospholipid. We further showed that S1P induces matriptase translocation and accumulation at cell-cell contacts where activation occurs, a process depending on the assembly of adherens junctions and formation of subcortical actin belts in response to Sip exposure. In the final year, we showed that both matriptase and HAI-1 are accumulated at activation foci during matriptase activation. The dual roles of HAI-i in matriptase activation and inhibition results in immediate inhibition of matriptase right after the activation of the protease. The close temporal and spatial coupling of matriptase activation with its inhibition suggests that the protealytic activity of this enzyme must be well controlled, and that the proteolysis of matriptase substrates may be tightly regulated by this mechanism.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA439289
Entities
People
- Chen-yong Lin
Organizations
- Georgetown University