Dipeptidyl peptidase IV (CD26) is a receptor for streptokinase on rheumatoid synovial fibroblasts
Plasminogen (Pg) binds to synovial fibroblasts from patients with rheumatoid arthritis with a very high affinity and in a dose-dependent manner. The Pg receptor in these cells is composed of a glycoprotein IIb/IIIa related protein (α(IIIb)β3) in association with dipeptidyl peptidase IV (DPP IV). Pg binds via its kringles to the β3 subunit of α(IIb)̄3, which is in the vicinity of receptor-bound urinary-type plasminogen activator (uPA). Activation of Pg to plasmin (Pm) by uPA induces a conformational change in the molecule, which facilitates the interaction of Pro-carbohydrate chains with DPP IV. This interaction induces a rise in cytosolic free Ca+2 concentration. The streptococcal Pg activator streptokinase (SK) also binds to rheumatoid synovial fibroblasts with high affinity and in a dose-dependent manner. By contrast, normal synovial fibroblasts do not bind SK. Cell-bound SK can activate Pg and induces a cytosolic Ca+2 mobilization which differs in nature from the response observed after activation by uPA. SK binding can be inhibited by fibronectin (FN), but not by Pg- or Pro-derived heavy chain. The receptor for SK was purified by affinity chromatography and identified as DPP IV. SK and FN bind to DPP IV via the amino acid sequence LTSRPA, common to both ligands. Our studies suggest that Pg/Pm binding to rheumatoid synovial fibroblasts can be regulated via two distinct types of binding sites on DPP IV. The first site involves direct binding via a lectin-like interaction. The second site functions in association with FN/SK. These findings suggest an important role of DPP IV in the regulation of Pg binding and activation on the surface of rheumatoid synovial fibroblasts.
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- Cardiovascular System & Hematology
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Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Cardiovascular System & Hematology