Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil inhibitory factor (NIF) is a hookworm-derived glycoprotein ligand of the integrin CD11b/CD18 that inhibits human neutrophil function (Moyle, M., Foster, D. L., McGrath, D. E., Brown, S. M., Laroche, Y., De Meutter, J., Stanssens, P., Bogowitz, C. A., Fried, V. A., Ely, J. A., Soule, H. R., and Vlasuk, G. P. (1994) J. Biol. Chem. 269, 1008-10015). Here, we present evidence that recombinant NIF (rNIF) associates with the approximately 200-amino acid residue I domain of CD11b/CD18 and that this interaction is essential for inhibition of neutrophil function by NIF. First, radiolabeled rNIF binds to a recombinant glutathione S-transferase fusion protein that contains the CD11b I domain. This high affinity interaction has a partial dependence on divalent cations. The association of rNIF with the CD11b I domain is specific because 125I-rNIF does not bind either a glutathione S-transferase fusion protein that contains the I domain of the integrin CD11a/CD18 or recombinant glutathione S-transferase without the I domain. Second, the CD11b I domain fusion protein effectively competes with CD11b/CD18 on human neutrophils for 125I-rNIF binding. Third, the CD11b I domain fusion protein blocks the inhibition of certain neutrophil functions by rNIF, including adhesion of neutrophils to human endothelial cell monolayers and adhesion-dependent release of hydrogen peroxide from neutrophils. Specificity is demonstrated by the inability of the CD11a I domain fusion protein to block either rNIF binding to neutrophils or rNIF activity. Fourth, rNIF blocks the interaction between neutrophils and fibrinogen, a CD11b/CD18 ligand that is also thought to bind the I domain of CD11b. In contrast, rNIF does not appear to block the binding of factor X to CD11b/CD18 on neutrophils. These results suggest that CD11b/CD18 has multiple distinct binding sites for its cognate ligands, including, but not limited to, the I domain. NIF interferes with the binding of a subset of these CD11b/CD18 ligands in a highly selective manner.
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PMID:Functional interaction between the integrin antagonist neutrophil inhibitory factor and the I domain of CD11b/CD18. 792 63

CD47-binding sequences from the carboxyl-terminal domain of thrombospondin-1 (TSP1) are known to regulate activity of the alpha(v)beta(3) integrin (Gao, G., Lindberg, F. P., Dimitry, J. M., Brown, E. J., and Frazier, W. A. (1996) J. Cell Biol. 135, 533-544). Here we show that peptides from the type 1 repeats of TSP1 also stimulate alpha(v)beta(3) integrin function in melanoma cells. Addition of soluble peptide 246 (KRFKQDGGWSHWSPWSS) enhances spreading of A2058 melanoma cells on several alpha(v)beta(3) integrin ligands, including vitronectin, recombinant TSP1 fragments containing the Arg-Gly-Asp sequence, and native TSP1. This activity requires the Trp residues and is independent of CD36-binding sequences in the type 1 repeats. Recombinant type 1 repeats expressed as a glutathione S-transferase fusion protein also enhance spreading on vitronectin and TSP1. Activation of alpha(v)beta(3) integrin by the soluble peptide 246 stimulates organization of F-actin and increases tyrosine phosphorylation of focal adhesion kinase. In contrast, direct adhesion of melanoma cells on immobilized peptide 246 inhibits tyrosine phosphorylation of focal adhesion kinase. Stimulation of alpha(v)beta(3) integrin function by the type 1 repeat peptide differs from that induced by CD47-binding TSP1 peptides in that heparan sulfate proteoglycans are required and pertussis toxin does not inhibit the former activity. Thus, the type 1 repeats contain a second sequence of TSP1 that can enhance alpha(v)beta(3) integrin signaling, and these two sequences stimulate recognition of both vitronectin and TSP1 by the alpha(v)beta(3) integrin.
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PMID:Cooperation between thrombospondin-1 type 1 repeat peptides and alpha(v)beta(3) integrin ligands to promote melanoma cell spreading and focal adhesion kinase phosphorylation. 1042 59