Cell-Surface Peptidases

Abstract

The cell surface has various functions: communicating with other cells, integrating into the tissue, and interacting with the extracellular matrix. Proteases play a key role in these processes. This review focuses on cell-surface peptidases (ectopeptidases, oligopeptidases) that are involved in the inactivation or activation of extracellular regulatory peptides, hormones, paracrine peptides, cytokines, and neuropeptides. The nomenclature of cell-surface peptidases is explained in relation to other proteases, and information is provided on membrane anchoring, catalytic sites, regulation, and, in particular, on their physiological and pharmacological importance. Furthermore, nonenzymatic (binding) functions and participation in intracellular signal transduction of cell surfaces peptidases are described. An overview on the different cell-surface peptidases is given, and their divergent functions are explained in detail. An example of actual pharmacological importance, dipeptidyl-peptidase IV (CD26), is discussed.

Dipeptidyl peptidase inhibitors as new drugs for the treatment of type 2 diabetes

“…DPP-IV is a pleiotropic enzyme that cleaves, and thereby generally inactivates, a variety of peptide hormones, neuropeptides and chemokines (reviewed in [16,17]). Furthermore, it acts as a binding protein for fibronectin and adenosine deaminase, and is a co-stimulator of T-cell activation.…”

“…Potential side-effects resulting from the prolongation of action of these messengers include neurogenic inflammation (substance P, neuropeptide Y), increases in blood pressure (neuropeptide Y), enhanced general inflammation, and allergic reactions (chemokines). However, to date, such side-effects have not been observed in preclinical animal or clinical human studies [17].…”

Heart Failure as a Comorbidity of Diabetes: Role of Dipeptidyl Peptidase 4

“…DPP4 (DPP4/DPPIV/CD26) is a 110-kDa type integral membrane glycoprotein that cleaves N-terminal dipeptides from peptides with preferably proline or alanine at the penultimate 62) . Interestingly, these substrates are bioactive peptides that regulate the cardiovascular system 63,64) (Fig.…”

Is Dipeptidyl Peptidase IV (DPP IV) Associated with Inflammation Present in Human Spondyloarthritides and Rheumatoid Arthritis?

“…7 Furthermore, it has been suggested that cell surface peptidases play an important role in the activation or inactivation of mediators involved in the occurrence and perpetuance of inflammatory processes. 8 Dipeptidyl peptidase IV (DPP IV; EC 3.4.14.5), known as CD26 molecule is a widely expressed multifunctional glycoprotein present both on the cell surface of various tissues and as a soluble form in plasma and other biological fluids. As a serine protease, DPP IV cleaves the N-terminal dipeptides from proteins having either proline or alanine at the penultimate position.…”