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 ddipeptidylpeptidase IV (DPP IV) activity, characteriz ed by its capacity to cleave off N-terminal dipeptides containing prol ine as the penultimate residue. Independent of its catalytic activity, CD26 has also been characterized as adenosine deaminase binding prote in. By using CD26 negative human C8166 cells, here we describe the exi stence of another cell-surface protein which manifests CD26-like DPP I V activity. For convenience, this protein will be referred to as DPP I V-beta. Consistent with the cell-surface expression of DPP IV-beta int act C8166 cells manifested a high level of DPP IV, whereas, they manif ested poor activity against substrates of DPP II known to have an intr acellular 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 additio n, cell-surface CD26 and DPP IV-beta on intact MOLT4 and C8166 cells, respectively, resisted digestion by proteolytic enzymes such as trypsi n and proteinase K. However, adenosine deaminase activity was not dete ctable on the surface of C8166 cells in contrast to CD26 positive MOLT 4 cells. In accord with this, I-125-labeled adenosine deaminase which binds CD26 was found not to bind DPP IV-beta. Gel-filtration experimen ts using 0.5 % Triton X-100 extracts from C8166 and MOLT4 cells, revea led 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 sugg est that DPP IV-beta is a CD26-like protein which could be characteriz ed by distinct properties.