Disease relevance of CD47/IAP

• Treatment of guinea pig neutrophils with pertussis toxin (islet-activating protein; IAP) results in inhibition of N-formyl peptide receptor-mediated release of arachidonic acid and granular enzymes [1].
• African swine fever virus IAP homologue inhibits caspase activation and promotes cell survival in mammalian cells [2].
• We conclude that in OA-injured lung, the increase of IAP increases the amount of edema [3].
• The ability of IAP to cause potentiation of insulin secretory responses and promotion of leukocytosis was studied in six animal species (hamsters, rats, guinea pigs, rabbits, dogs and monkeys) [4].
• Two ASFV proteins, an IAP and a Bcl2 homologue, inhibit apoptosis in infected cells and thus facilitate production of progeny virions [5].

High impact information on CD47/IAP

• The association between integrin-associated protein and SHPS-1 regulates insulin-like growth factor-I receptor signaling in vascular smooth muscle cells [6].
• Disruption of IAP-SHPS-1 binding, by using an IAP monoclonal antibody or cells expressing mutant forms of IAP that did not bind to SHPS-1, inhibited IGF-I-stimulated SHPS-1 phosphorylation and SHP-2 recruitment [6].
• Thus, 1) the LTD4 receptor is coupled to an IAP-sensitive GTP-binding protein, 2) this GTP-binding protein is dissociable from the receptor by solubilizing the lung membrane with CHAPS and Mg2+, and 3) the receptor associated to or dissociated from a GTP-binding protein exhibited a high- or low-affinity state, respectively [7].
• Consistently, a 41-kDa protein was ADP-ribosylated by treatment of the lung membranes with IAP, and this event was inhibited by the addition of GTP gamma S. We solubilized the LTD4 receptor from the lung membranes in an active form with 5 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and 10% glycerol [7].
• In the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) or by prior treatment of the membrane with islet-activating protein (IAP), the high-affinity site shifted to a low-affinity state [7].

Chemical compound and disease context of CD47/IAP

• These early responses of neutrophils to fMet-Leu-Phe, eventually leading to O2- generation, were abolished by prior exposure of cells to islet-activating protein (IAP), pertussis toxin, which had been reported to bring about ADP-ribosylation of a membrane Mr = 41,000 protein (Okajima, F., and Ui, M. (1984) J. Biol. Chem. 259, 13863-13871) [8].
• This increase was inhibited in cells that were pretreated with islet-activating protein (IAP, pertussis toxin) or N-ethylmaleimide (NEM) [9].
• In an attempt to identify the nature of guanine nucleotide binding protein(s) (G-protein) involved in the acetylcholine (ACh)-induced (muscarinic) response of pig coronary-artery smooth muscle, we studied the effect of ADP-ribosylation of specific membrane protein(s) catalysed by islet-activating protein (IAP; pertussis toxin) [10].
• Bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells was enhanced by pretreatment of the cells with pertussis toxin or islet-activating protein (IAP) for 5 hr or longer [11].
• Islet-activating protein (IAP), one of the pertussis toxins, serving [alpha-32P]nicotinamide adenine dinucleotide (NAD) as a substrate for ADP ribosylation, radiolabelled a specific pig epidermal membrane protein [12].

Biological context of CD47/IAP

• It is proposed that in neutrophils the IAP substrate, which is a subunit of the guanine nucleotide regulatory protein involved in adenylate cyclase inhibition in a variety of other cell types, plays an essential role in the Ca2+-mobilizing receptor-mediated signal transduction system, conceivably in processes proximal to Ca2+ gating [13].
• African swine fever virus (ASFV) A224L is a member of the inhibitor of apoptosis protein (IAP) family [2].
• A pretreatment of the receptor-GTP binding protein complex with islet-activating protein (IAP) increased the inhibitory effect of GTP gamma S on LTB4 binding, indicating that the LTB4 receptor is coupled with an IAP-sensitive GTP-binding protein in the porcine spleen [14].
• CNAP significantly (p<0.05) decreased IAP (30.7+/-1.3 to 18.2+/-1.3), central venous pressure (15.2+/-1.7 to 12.4+/-2.1), inferior vena cava (29.5+/-1.5 to 19.2+/-1.3), and ICP (21.0+/-1.5 to 16.2+/-1.3) [15].

Anatomical context of CD47/IAP

• The IAP component of pertussis toxin blocked the inhibitory action of InP-gly on cAMP accumulation by reconstituted thyroid follicles (RTF), suggesting the participation of Gi protein [16].
• Although ADP-ribosylation of a protein with a molecular weight of 41-42 kD in the cell membranes was completed by 3 hr after the addition of IAP into the incubation medium, there was good correlation between enhancement of bradykinin-induced prostacyclin synthesis and ADP-ribosylation of the IAP substrate over a wide range of IAP concentrations [11].
• METHODS: Anesthetized, ventilated swine had catheters placed for measurement of intra-abdominal (IAP), intracranial (ICP), central venous, pulmonary artery, pulmonary artery occlusion, mean arterial, peak inspiratory, inferior vena cava, and femoral vein pressures [15].
• These results suggest that IAP may inhibit H3 receptors in the ileum at similar concentrations reported to inhibit H2 receptors in functional studies [17].
• IAP was increased by incrementally instilling an isosmotic polyethylene glycol solution into the peritoneal cavity until it was 25 mm Hg above baseline [15].

Associations of CD47/IAP with chemical compounds

• Release of arachidonic acid and accumulation of inositol 1-monophosphate in delayed response to fMet-Leu-Phe were also abolished by the IAP treatment of cells, despite the fact that slowly-onset inflow of Ca2+ which must be responsible for these delayed responses was observed in these IAP-treated cells [8].
• In contrast to the responses to the chemotactic peptide, similar responses of neutrophils to A23187, a Ca2+ ionophore, were not affected by the prior treatment of the cells with IAP [13].
• The agonist-independent, GTP-induced activation of IK.ACh was inhibited by the A promoter of IAP (with nicotinamide adenine dinucleotide) or NEM [9].
• In intact tissues, pretreatment with up to 100 ng of IAP/ml inhibited neither the ACh-induced decrease in the amount of inositol phospholipids nor the increase in the amounts of phosphatidic acid and of inositol phosphates [10].
• IAP treatment increased the amount of cyclic AMP accumulated by isoprenaline [10].

Physical interactions of CD47/IAP

• Integrin-associated protein binding domain of thrombospondin-1 enhances insulin-like growth factor-I receptor signaling in vascular smooth muscle cells [18].

Analytical, diagnostic and therapeutic context of CD47/IAP

• Western and Northern blot analyses revealed that IAP decreased the amounts of protein and mRNA of lipocortin I [11].
• However, in patients in whom an increased IAP does not require surgical decompression, the results of this study suggest that externally applied CNAP may be of value [15].
• All parameters were remeasured 30 minutes after each increase in IAP, at 2 hours after attaining maximum IAP, and lastly at 2 hours after abdominal decompression [15].

References