CAP37, a neutrophil granule-derived protein stimulates protein kinase C activity in endothelial cells.
CAP37 is a multifunctional protein isolated from human neutrophils with important implications in host defense and inflammation. It is antimicrobial, mediates monocyte chemotaxis, and binds endotoxin. The interaction of neutrophils with endothelial cells is a central feature in inflammation. The object of this study was to determine whether CAP37, a neutrophil-derived protein, could regulate vascular endothelial cell protein kinase C (PKC), an important signaling enzyme. We found that CAP37 stimulated endothelial PKC activity in both a time- and dose-dependent fashion. This stimulation was comparable in magnitude to that evoked by phorbol myristate acetate. A monospecific antiserum against CAP37 inhibited CAP37-induced PKC activity. To establish a structural basis for this activity, overlapping peptides, based on the sequence of native CAP37 were synthesized. Maximum PKC stimulation was evoked by a peptide corresponding to amino acids 95-122 of native CAP37. This domain was distinct from the antibiotic and endotoxin binding domain of the molecule, which resides between amino acids 20 and 44. These data demonstrate that CAP37 can alter endothelial cell PKC and suggest that CAP37 may play a role in neutrophil-endothelial interactions.
Pereira
H A
HA
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Moore
P
P
Grammas
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D023181:Antimicrobial Cationic Peptides; D001665:Binding Sites; D001798:Blood Proteins / Q000276:immunology / Q000494:pharmacology*; D002352:Carrier Proteins; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010449:Peptide Mapping; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D010446:Peptide Fragments; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate