The mouse macrophage activation-associated marker protein, p71/73, is an inducible prostaglandin endoperoxide synthase (cyclooxygenase).
The inducible protein p71/73 marks the response of mouse macrophages to one of several stimuli (e.g., bacterial lipopolysaccharide or poly I:C) that trigger the expression of cytolytic activity when these cells have previously been primed for tumor cell killing by interferon-gamma (IFN-gamma). The results reported here identify this marker protein as the inducible prostaglandin endoperoxide synthase (PES), TIS10/PES-2. Identification was based on four findings: (1) p71/73, like the TIS10/PES-2 protein, was associated with cellular membranes; (2) the sequence of amino acids in the NH2 terminus of both p71 and p73 was 96% identical to the predicted NH2-terminal sequence of the TIS10/PES-2 protein; (3) a polyclonal antiserum raised against the COOH-terminal region of the TIS10/PES-2 gene product recognized p71/73 in immunoblots; and (4) dexamethasone, which blocks induction of TIS10/PES-2 expression, inhibited the induction of both p71/73 synthesis and tumoricidal activity in macrophage. Several regulatory roles for this protein in the activation process are possible.
Phillips
T A
TA
Wilkinson Laboratory of the Cancer Center, University of Kansas Medical Center, Kansas City 66160-7184.
Kujubu
D A
DA
MacKay
R J
RJ
Herschman
H R
HR
Russell
S W
SW
Pace
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D015415:Biomarkers; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002645:Chickens; D003594:Cytoplasmic Granules / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D006801:Humans; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D012756:Sheep
D000906:Antibodies; D015415:Biomarkers; D008070:Lipopolysaccharides; D010455:Peptides; D011451:Prostaglandin-Endoperoxide Synthases