The S100 family protein MRP-14 (S100A9) has homology with the contact domain of high molecular weight kininogen.
The heterodimeric molecule MRP-8/MRP-14 (S100A8/S100A9) is abundantly expressed in circulating monocytes and neutrophils. We report here an homology between the C-terminal 'tail' region of MRP-14 (S100A9) and sequences within the plasma protein, high molecular weight kininogen (HMWK) which are involved in binding to negatively charged surfaces such as kaolin. MRP-14 also binds to kaolin and is competitively inhibited by HMWK and by peptides corresponding to MRP-14 tail and the HMWK 'contact' regions. Furthermore both MRP-14 and the tail peptide inhibit the coagulation cascade in vitro giving functional relevance to the homology between MRP-14 and HMWK. At inflammatory sites, MRP-8/14 is localised to areas of close contact between myeloid cells and endothelium. The results of this study identify a potential binding region in MRP-14 and suggest that it could function by interfering with fibrin formation at sites of leukocyte transendothelial migration.
Hessian
P A
PA
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, London, UK.
Wilkinson
L
L
Hogg
N
N
D000595:Amino Acid Sequence; D000838:Anions / Q000378:metabolism; D000943:Antigens, Differentiation / Q000737:chemistry*; D001665:Binding Sites; D001777:Blood Coagulation; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D040502:Calgranulin B; D007616:Kaolin / Q000378:metabolism; D007704:Kininogens / Q000737:chemistry*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D000838:Anions; D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040502:Calgranulin B; D007704:Kininogens; D007616:Kaolin