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. In non-transformed mammary epithelial cells, matriptase activation can be induced by sphingosine 1-phosphate, a blood-borne bloactive phospholipid. In addition to S1P, as an exogenous inducer, both catalytic and non-catalytic domains of matriptase could also participate in the activation of the protease. In the past one-year, we have systemically constructed matriptase mutants, and used these mutants to study the structural requirements for matriptase activation. Our data reveal that matriptase activation requires its own catalytic activity, 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 (LDL) receptor. Its cognate inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), may also participate in the activation of matriptase. These results suggest that besides matriptase catalytic activity, matriptase activation requires posttranslational modification of the protease, intact non-catalytic domain, and its cognate inhibitor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417787
Entities
People
- Chen-yong Lin
Organizations
- Georgetown University