Conditioning response to granulocyte colony-stimulating factor via the dipeptidyl peptidase IV-adenosine deaminase complex

Focosi, Daniele; Kast, Richard E.; Galimberti, Sara; Petrini, Mario

doi:10.1189/jlb.0208109

Cited by 6 publications

(4 citation statements)

References 104 publications

(115 reference statements)

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“…These authors also indicated that the optimal pH of CD26 activity in the CD26–ADA complex is more alkaline than the physiological pH described for CD26. These results have been interpreted as showing that ADA raises the local pH by locally generating ammonia and increases CD26 efficiency in the CD26–ADA binary complex …”

Section: Cell Surface Ada As a Costimulatory Molecule With Implicatiomentioning

confidence: 92%

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

Cortés

Gracia

Moreno

et al. 2014

Medicinal Research Reviews

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Interest in adenosine deaminase (ADA) in the context of medicine has mainly focused on its enzymatic activity. This is justified by the importance of the reaction catalyzed by ADA not only for the intracellular purine metabolism, but also for the extracellular purine metabolism as well, because of its capacity as a regulator of the concentration of extracellular adenosine that is able to activate adenosine receptors (ARs). In recent years, other important roles have been described for ADA. One of these, with special relevance in immunology, is the capacity of ADA to act as a costimulator, promoting T-cell proliferation and differentiation mainly by interacting with the differentiation cluster CD26. Another role is the ability of ADA to act as an allosteric modulator of ARs. These receptors have very general physiological implications, particularly in the neurological system where they play an important role. Thus, ADA, being a single chain protein, performs more than one function, consistent with the definition of a moonlighting protein. Although ADA has never been associated with moonlighting proteins, here we consider ADA as an example of this family of multifunctional proteins. In this review, we discuss the different roles of ADA and their pathological implications. We propose a mechanism by which some of their moonlighting functions can be coordinated. We also suggest that drugs modulating ADA properties may act as modulators of the moonlighting functions of ADA, giving them additional potential medical interest.

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Section: Cell Surface Ada As a Costimulatory Molecule With Implicatiomentioning

confidence: 92%

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

Cortés

Gracia

Moreno

et al. 2014

Medicinal Research Reviews

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“…DPP4 recruits ADA, a monomeric enzyme catalyzing deamination of adenosine to inosine and ammonia ( 121 , 122 ). It has been shown that DPP4-bound ADA has a 1000-fold greater activity than free ADA ( 123 ), which in turn may modulate the well-established antilipolytic effects of adenosine. Moreover, DPP4 is a strong inhibitor of the antilipolytic activity of NPY ( 76 ), which is one of the best peptide substrates of the enzyme ( 89 ).…”

Section: Impact Of Dpp4 On T2dm-relevant Organs and Associated Comorbmentioning

confidence: 99%

DPP4 in diabetes

2015

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Dipeptidyl-peptidase 4 (DPP4) is a glycoprotein of 110 kDa, which is ubiquitously expressed on the surface of a variety of cells. This exopeptidase selectively cleaves N-terminal dipeptides from a variety of substrates, including cytokines, growth factors, neuropeptides, and the incretin hormones. Expression of DPP4 is substantially dysregulated in a variety of disease states including inflammation, cancer, obesity, and diabetes. Since the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP), are major regulators of post-prandial insulin secretion, inhibition of DPP4 by the gliptin family of drugs has gained considerable interest for the therapy of type 2 diabetic patients. In this review, we summarize the current knowledge on the DPP4–incretin axis and evaluate most recent findings on DPP4 inhibitors. Furthermore, DPP4 as a type II transmembrane protein is also known to be cleaved from the cell membrane involving different metalloproteases in a cell-type-specific manner. Circulating, soluble DPP4 has been identified as a new adipokine, which exerts both para- and endocrine effects. Recently, a novel receptor for soluble DPP4 has been identified, and data are accumulating that the adipokine-related effects of DPP4 may play an important role in the pathogenesis of cardiovascular disease. Importantly, circulating DPP4 is augmented in obese and type 2 diabetic subjects, and it may represent a molecular link between obesity and vascular dysfunction. A critical evaluation of the impact of circulating DPP4 is presented, and the potential role of DPP4 inhibition at this level is also discussed.

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“…Drugs affecting CD26 that could be used in the clinic to augment the mobilizing effects of G-CSF have been reviewed [97]. Other proteases have also been implicated in HSPC mobilization.…”

Section: Mobilizationmentioning

confidence: 99%

“…As the major function of CD26 is to cleave the N-terminal of SDF-1, inhibition of CD26 on HSPC increases their SDF-directed chemotaxis in vitro and their in vivo homing and engraftment [187]. In fact, sitagliptin, an oral inhibitor of CD26, has been used clinically and has resulted in speedy engraftment of HSPC [97]. …”

Section: Homingmentioning

confidence: 99%

The Ins and Outs of Hematopoietic Stem Cells: Studies to Improve Transplantation Outcomes

Marquez‐Curtis

Turner

Sridharan

et al. 2010

Stem Cell Rev and Rep

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Deciphering the mechanisms of hematopoietic stem/progenitor cell (HSPC) mobilization and homing is important for the development of strategies to enhance the efficacy of HSPC transplantation and achieve the full potential of HSPC-based cellular therapy. Investigation of these mechanisms has revealed interdependence among the various molecules, pathways and cellular components involved, and underscored the complex nature of these two processes. This review summarizes recent progress in identifying the specific factors implicated in HSPC mobilization and homing, with emphasis on our own work. Particularly, we will discuss our studies on stromal cell-derived factor-1 and its interaction with its receptor CXCR4, proteases (matrix metalloproteinases and carboxypeptidase M), complement proteins (C1q, C3a, C5a, membrane attack complex), sphingosine-1-phosphate, and pharmacologic agents such as the histone deacetylase inhibitor valproic acid and hyaluronic acid.

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Conditioning response to granulocyte colony-stimulating factor via the dipeptidyl peptidase IV-adenosine deaminase complex

Cited by 6 publications

References 104 publications

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

DPP4 in diabetes

The Ins and Outs of Hematopoietic Stem Cells: Studies to Improve Transplantation Outcomes

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