Background: The ␣6␤4 integrin assembles via an unknown mechanism with receptor tyrosine kinases. Results: HER2-dependent activation of ␣6␤4 depends on capture of the ␤4 cytoplasmic domain by syndecan-1, whereas HER1 (EGFR) relies on syndecan-4. Conclusion: Cell invasion and survival mediated by the ␣6␤4 integrin depend on its assembly with kinase-specific syndecans. Significance: These novel interactions may provide targets for new therapeutics to combat carcinogenesis.

Background:The ␣6␤4 integrin associates with syndecans and, via an unknown mechanism, with receptor tyrosine kinases. Results: Syndecans-1 and -4 capture HER2 and EGFR, along with ␣3␤1 integrin, via docking sites in their ectodomains. Conclusion: Syndecans organize integrins and receptor tyrosine kinases into signaling complexes that stimulate epithelial invasion. Significance: Novel peptides (synstatins) are defined that block kinase capture and are potential cancer therapeutics.

A cDNA encoding a protein resembling masquerade, a serine proteinase homologue expressed during embryogenesis, larval, and pupal development in Drosophila melanogaster, was identified in hemocytes of the adult freshwater crayfish, Pacifastacus leniusculus. The crayfish protein is similar to Drosophila masquerade in the following aspects: (a) overall sequence of the serine proteinase domain, such as the position of three putative disulfide bridges, glycine in the place of the catalytic serine residue, and the presence of a substrate-lining pocket typical for trypsins; (b) the presence of several copies of a disulfide-knotted motif in the putative propeptide. This masquerade-like protein is cleaved into a 27-kDa fragment, which could be detected by immunoblot analysis using an affinity-purified antibody against a synthetic peptide in the C-terminal domain of the protein. The 27-kDa protein could be immunoaffinity-purified from hemocyte lysate supernatant and exhibited cell adhesion activity in vitro, indicating that the C-terminal domain of the crayfish masquerade-like protein mediates cell adhesion.

Our earlier study in vivo showed that a lower dose of acetylsalicylic acid (ASA) brought greater enhancement in fibrin gel permeability (Ks) than a higher dose. To assess whether this finding related to modifications of fibrinogen clotting property by ASA, purified fibrinogen was incubated with ASA and/or salicylic acid (SA). The fibrinogen product was examined. Fibrinogen "clotting time" was not affected. Shortening of fibrin clot "lysis time" paralleled the increase of fibrin network porosity demonstrated by measurements of liquid permeability (Ks), fibrin fiber thickness, and 3-dimensional microscopic image, in a low ASA concentration-dependent way. Ks levels were not altered by SA alone but significantly decreased in samples treated by both where the concentrations were low for ASA and high for SA. In conclusion, ASA at the concentrations used did not influence the rate of fibrinogen gelation by thrombin. However, assembly of fibrin monomers was most probably altered, leading to enhancement of fibrin fiber thickness. A looser network was constructed by the thicker fibrin fibers, which benefits fibrinolysis. According to the known mechanism that SA interferes with ASA in preventing acetylation of platelet's proteins, an explanation for the low ASA concentration-dependent effects on fibrin network structure may be that fewer molecules of SA-the hydrolytic product of ASA-are generated from lower doses of ASA, which block acetylation of fibrinogen to a smaller extent and thus more significantly impair fibrin formation.