Dipeptidyl-peptidase IV-beta, a novel form of cell-surface-expressed protein with dipeptidyl-peptidase IV activity.
The T-cell activation antigen CD26, is a type II membrane glycoprotein with intrinsic dipeptidyl-peptidase IV (DPP IV) activity, characterized by its capacity to cleave off N-terminal dipeptides containing proline as the penultimate residue. Independent of its catalytic activity, CD26 has also been characterized as adenosine deaminase binding protein. By using CD26 negative human C8166 cells, here we describe the existence of another cell-surface protein which manifests CD26-like DPP IV activity. For convenience, this protein will be referred to as DPP IV-beta. Consistent with the cell-surface expression of DPP IV-beta, intact C8166 cells manifested a high level of DPP IV, whereas, they manifested poor activity against substrates of DPP II known to have an intracellular localization. A partially purified preparation of CD26 from human MOLT4 cells, and the DPP IV-beta expressed on intact cells were found to possess similar catalytic activity and pH optimum. In addition, cell-surface CD26 and DPP IV-beta on intact MOLT4 and C8166 cells, respectively, resisted digestion by proteolytic enzymes such as trypsin and proteinase K. However, adenosine deaminase activity was not detectable on the surface of C8166 cells in contrast to CD26 positive MOLT4 cells. In accord with this, 125I-labeled adenosine deaminase which binds CD26 was found not to bind DPP IV-beta. Gel-filtration experiments using 0.5% Triton X-100 extracts from C8166 and MOLT4 cells, revealed that the apparent molecular mass of DPP IV-beta is 82 kDa, whereas that of CD26 is 110 kDa as expected. Taken together, our results suggest that DPP IV-beta is a CD26-like protein which could be characterized by distinct properties.
Jacotot
E
E
Unité de Virologie et Immunologie Cellulaire, UA CNRS 1157, Institut Pasteur, Paris, France.
Callebaut
C
C
Blanco
J
J
Krust
B
B
Neubert
K
K
Barth
A
A
Hovanessian
A G
AG
D000243:Adenosine Deaminase / Q000378:metabolism; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002850:Chromatography, Gel; D002855:Chromatography, Thin Layer; D004151:Dipeptides; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D008970:Molecular Weight; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004151:Dipeptides; D007527:Isoenzymes; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase