During the past year we have: (a) demonstrated that phospholipase A2 (PLA2) is activated by transglutaminase (TG) and factor XIIIa-mediated polyamination of this enzyme; (b) developed a monospecific antibody that completely inhibits the activity of PLA2 and identified a specific region of this enzyme (residues 21-40) which interacts with the neutralizing antibody; (c) expressed recombinant human cc10kDa protein at high level in E. coli. purified this protein to homogeneity and demonstrated that this protein is a potent inhibitor of PLA2 activity as well as that it is a substrate of TG; (d) demonstrated that cc10kDa gene is expressed in various tissues and cells other than the pulmonary alveolar Clara cells as was originally thought; (e) discovered that surfactant-producing rabbit pulmonary alveolar type II cells synthesize and secrete UG, thereby protecting the phospholipid component of the surfactant; (f) delineated a specific region of osteopontin (OP) which is the calcium binding site of this protein; (g) shown that in the milk of mothers who delivered premature infants, the OP level is significantly higher than in the milk of mothers who delivered at term suggesting a possible role of OP in calcium transport from other to the neonate; (h) discovered a novel TG-mediated posttranslational modification of OP which may enhance its interaction with fibronectin, an extracellular matrix (ECM) protein; (i) discovered a novel splicing of OP mRNA with possible regulatory role in transcriptional and/or posttranscriptional events, possibly explaining the multifunctional role of OP in diverse cell types and tissues; (j) demonstrated a TG-mediated polyamination of HIV-1 protease, similar to the ones observed for PLA2, which may have implication for its activation; (k) developed a rapid and simple radiometric assay for HIV-1 aspartyl protease (HIV-1 AP) for screening of potential inhibitors of this enzyme; (l) developed monoclonal antibodies of AP which inhibit its activity. A patent application for the radiometric assay of HIV-1 AP has been filed and a CRADA on further characterization and development of this assay has been established.
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