Biomaterial Database

Amino-terminal processing of MIP-1beta/CCL4 by CD26/dipeptidyl-peptidase IV. 2004

Ennan Guan, and Jinhai Wang, and Michael A Norcross

Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. guan@cber.fda.gov

CD26 is a membrane-bound ectopeptidase with dipeptidyl peptidase IV (DPPIV) activity that has diverse functional properties in T cell physiology and in regulation of bioactive peptides. We have previously reported that activated human peripheral lymphocytes (PBL) secrete an amino-terminal truncated form of macrophage inflammatory protein (MIP)-1beta/(3-69) with novel functional specificity for CCR1, 2, and 5. In this report, we show that the full length MIP-1beta is processed by CD26/DPPIV to the truncated form and that cleavage can be blocked by DPPIV inhibitory peptides derived from HIV Tat(1-9) or the thromboxane A2 receptor, TAX2-R(1-9). Addition of Tat(1-9) or TAX2-R(1-9) peptides to PBL cultures partially blocks endogenous MIP-1beta processing. The kinetics of conversion of MIP-1beta from intact to MIP-1beta(3-69) in activated PBLs correlates with cell surface expression of CD26. Our results suggest that NH2-terminal processing of MIP-1beta and possibly other chemokines may depend on the balance between CD26/DPPIV enzymatic activity and cellular and viral proteins that modulate enzyme function.

UI	MeSH Term	Description	Entries
D008214	Lymphocytes	White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.	Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D009000	Monocytes	Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.	Monocyte
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013058	Mass Spectrometry	An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.	Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass
D015696	Gene Products, tat	Trans-acting transcription factors produced by retroviruses such as HIV. They are nuclear proteins whose expression is required for viral replication. The tat protein stimulates LONG TERMINAL REPEAT-driven RNA synthesis for both viral regulatory and viral structural proteins. Tat stands for trans-activation of transcription.	tat Gene Products,tat Protein,Gene Product, tat,tat Gene Product
D044244	Receptors, Thromboxane A2, Prostaglandin H2	A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.	Prostaglandin H2 Receptor,Receptors, Prostaglandin H2,Receptors, TXA2-PGH2,Receptors, Thromboxane A2,TXA2-PGH2 Receptors,Thromboxane A2, Prostaglandin H2 Receptors,PGH2 Receptors,Thromboxane A2 Receptor,H2 Receptors, Prostaglandin,Prostaglandin H2 Receptors,Receptor, Prostaglandin H2,Receptors, PGH2,Receptors, TXA2 PGH2,TXA2 PGH2 Receptors
D047468	Immunoprecipitation	The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.	Co-Immunoprecipitation,Immune Precipitation,Co Immunoprecipitation,Co-Immunoprecipitations,Immune Precipitations,Precipitation, Immune,Precipitations, Immune