5. Conclusions
The biological significance of the new DPIV family members DP8 and DP9 is unknown. In order to obtain correlations between cell behaviors and peptidase expression levels, DP8 and DP9 overexpression in transfected cells was quantified by expressing green fluorescent protein fusion proteins. We found that, like DPIV and FAP, cells overexpressing DP8 and DP9 exhibit behavioral changes in the presence of ECM components. We demonstrated that these effects were independent of enzyme activity, and of the RGD motif that occurs in DP9. This study is the first indication of some similarities as well as differences between DP8, DP9, DPIV and FAP in their cell biological roles.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abbott CA, McCaughan GW, Gorrell MD, 1999, Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity. FEBS Lett. 458: 278–284.
Abbott CA, Yu DMT, Woollatt E, Sutherland GR, McCaughan GW, Gorrell MD, 2000, Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8. Eur J Biochem. 267: 6140–6150.
Ajami K, Abbott CA, Obradovic M, Gysbers V, Kähne T, McCaughan GW, Gorrell MD, 2003, Structural requirements for catalysis, expression and dimerisation in the CD26/DPIV gene family. Biochemistry. 42: 694–701.
Ajami K, Abbott CA, McCaughan GW, Gorrell MD, 2004, Dipeptidyl peptidase 9 is cytoplasmic and has two forms, a broad tissue distribution, cytoplasmic localization and DPIV—like peptidase activity. BBA—Gene Struct Expression. 1679: 18–28.
Alahari SK, Lee JW, Juliano RL, 2000, Nischarin, a novel protein that interacts with the integrin alpha5 subunit and inhibits cell migration. J Cell Biol. 151: 1141–1154.
Cheng HC, Abdel-Ghany M, Pauli BU, 2003, A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis. J Biol Chem. 278: 24600–24607.
Gorrell MD, 2003, First bite. Nat Struct Biol. 10: 3–5.
Gorrell MD, Yu DMT, 2005, Diverse functions in a conserved structure: The dipeptidyl peptidase IV gene family. Trends in Protein Research. Edited by Robinson JW. New York, Nova Biomedical Books pp. 1–78.
Huttenlocher A, Lakonishok M, Kinder M, Wu S, Truong T, Knudsen KA, Horwitz AF, 1998, Integrin and cadherin synergy regulates contact inhibition of migration and motile activity. J Cell Biol. 141: 515–526.
Hynes RO, 2002, Integrins: bidirectional, allosteric signaling machines. Cell 110: 673–687.
Itoh Y, Takamura A, Ito N, Maru Y, Sato H, Suenaga N, Aoki T, Seiki M, 2001, Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion. EMBO J. 20: 4782–4793.
Khin EE, Kikkawa F, Ino K, Kajiyama H, Suzuki T, Shibata K, Tamakoshi K, Nagasaka T, Mizutani S, 2003, Dipeptidyl peptidase IV expression in endometrial endometrioid adenocarcinoma and its inverse correlation with tumor grade. Am J Obstet Gynecol. 188: 670–676.
Levy MT, McCaughan GW, Abbott CA, Park JE, Cunningham AM, Rettig WJ, Gorrell MD, 1999, Fibroblast activation protein: A cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis. Hepatology. 29: 1768–1778.
Levy MT, McCaughan GW, Marinos G, Gorrell MD, 2002, Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infection. Liver. 22: 93–101.
Matsumoto Y, Bishop GA, McCaughan GW, 1992, Altered zonal expression of the CD26 antigen (dipeptidyl peptidase IV) in human cirrhotic liver. Hepatology 15: 1048–1053.
Matsuyama W, Wang L, Farrar WL, Faure M, Yoshimura T, 2004, Activation of discoidin domain receptor 1 isoform b with collagen up-regulates chemokine production in human macrophages: role of p38 mitogen-activated protein kinase and NF-kappa B. J Immunol. 172: 2332–2340.
Mueller SC, Ghersi G, Akiyama SK, Sang QXA, Howard L, Pineiro-Sanchez M, Nakahara H, Yeh Y, Chen WT, 1999, A novel protease-docking function of integrin at invadopodia. J Biol Chem. 274: 24947–24952.
Nusrat A, Delp C, Madara JL, 1992, Intestinal epithelial restitution. Characterization of a cell culture model and mapping of cytoskeletal elements in migrating cells. J Clin Invest 89: 1501–1511.
Pethiyagoda CL, Welch DR, Fleming TP, 2001, Dipeptidyl peptidase IV (DPPIV) inhibits cellular invasion of melanoma cells. Clin Exp Metastasis. 18: 391–400.
Qi SY, Riviere PJ, Trojnar J, Junien JL, Akinsanya KO, 2003, Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases. Biochem J. 373: 179–189.
Spizz G, Blackshear PJ, 2001, Overexpression of the myristoylated alanine-rich C-kinase substrate inhibits cell adhesion to extracellular matrix components. J Biol Chem. 276: 32264–32273.
Tanaka S, Murakami T, Horikawa H, Sugiura M, Kawashima K, Sugita T, 1997, Suppression of arthritis by the inhibitors of dipeptidyl peptidase IV. Int J Immunopharmacol. 19: 15–24.
Wesley UV, Tiwari S, Houghton AN, 2004, Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells. Int J Cancer. 109: 855–866.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer Science+Business Media, Inc.
About this paper
Cite this paper
Yu, D.M.T., Wang, X.M., Ajami, K., McCaughan, G.W., Gorrell, M.D. (2006). DP8 and DP9 have Extra-Enzymatic Roles in Cell Adhesion, Migration and Apoptosis. In: Lendeckel, U., Reinhold, D., Bank, U. (eds) Dipeptidyl Aminopeptidases. Advances in Experimental Medicine and Biology, vol 575. Springer, Boston, MA . https://doi.org/10.1007/0-387-32824-6_7
Download citation
DOI: https://doi.org/10.1007/0-387-32824-6_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-29058-4
Online ISBN: 978-0-387-32824-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)