By Carmen Mrestani-Klaus, Susan Lorey, Jürgen Faust, Frank Bühling (auth.), Jürgen Langner, Siegfried Ansorge (eds.)
The notion to bring together fresh effects at the ectoenzymes aminopeptidase N/CD13 and dipeptidylpeptidase IV/CD26 arose from the good curiosity given by way of readers world-wide to the 2 court cases volumes edited through us in 1997 and 2000 (Ansorge and Langner, 1997; Langner and Ansorge, 2000). those volumes contained the displays at symposia held in Magdeburg (Germany) in 1996 and 1999 below the name "Cellular peptidases in immune features and diseases", which used to be additionally the identify of the Sonderforschungsbereich in Magdeburg, backed by way of the Deutsche Forschungsgemeinschaft among 1995 and 2001. Our teams in Magdeburg and Halle over the past twenty years have supplied effects on those enzymes in cells of the hematopoietic process that justify a evaluate in an edited monograph just like the current one (see the experiences by means of Kahne et at. , 1999; Lendeckel et at. ,1999; Riemann et at. , 1999). There are, notwithstanding, many different teams in Europe, US and Japan which made very important contributions to this box and especially in themes bettering the knowledge of physiological and pathophysiological roles ofAPN/CD13 and DPIV/CD26. accordingly we determined to ask a few of them to give a contribution stories in their effects to this e-book. Having labored for roughly forty years within the box of proteolysis, for either one of us to determine the advance of actions and data from protein chemistry and enzymology to body structure and pathophysiology or even to treatment is especially stimulating and interesting. in fact, this improvement additionally displays the dramatic development and refinement of methods.
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Additional info for Ectopeptidases: CD13/Aminopeptidase N and CD26/Dipeptidylpeptidase IV in Medicine and Biology
The possible coupling of APN to ion channels needs further investigation. 36 5. LENDECKEL et al MUTATIONS IN THE HUMAN APN GENE A significant fraction of malignant lymphocytes and corresponding cell lines appear CD13-positive in flow cytometry. In addition, "CD13-negative" T and B cell lines were shown to contain considerable amounts of APN mRNA (Lendeckel et al 1996). Therefore, it was suggested that a dysregulation of APN expression contributes to or results from malignant transformation of lymphocytes and/or cellular growth.
I1c 1I"c --I~ I I I I I I I I I I I I I I I I I I I I I I I I A ____ I ,W...... :rrc c B :uv..... _~ , .......... , . CltJOL I Figure 7: Fluorescence on DPIV-rich U937 cells after incubation with substrates of the structure Xaa-Pro-RllO-Y. A to D represent the differences of the directly measured cellassociated fluorescence as well as after one to four wash steps. , Y2, Y3, Y6 ; cf. Table 2 and Fig. 5). , B: Y =Y2, C: Y =Y6, comparable with Y7, Yg and Y9, D: Y = Y 3, comparable with Y4 and Y5. 2, incubation 30 min, 37°C; U937 cells: 106 celis/mI, [Xaa-Pro-RIlO-Yl = 5 .
6), confirming the results of the co-localization studies, which showed a clear ER-retardation of these proteins. Furthermore, the neutral aminopeptidase activity of the wild type enzyme was fully preserved in APN-GFP. 7 % of the activity of cells transfected with wild type APN-GFP. 05), representing a decrease of wild type activity back to the control level (48 %) (Fig. 7). The results of this study clearly show that the deletion of the proline residue 227 from APN (LU27P) and the substitution of proline for Leu243, as observed in patients suffering from acute lymphatic leukemia of B cell type (B-ALL) or non-Hodgkin lymphoma (NHL) (Lendeckel et al 1998) result in a completely enzymatically inactive APN.