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| CALMODULIN IS A SUBUNIT OF NITRIC-OXIDE SYNTHASE FROM MACROPHAGES |
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| Author(s): CHO HJ, XIE QW, CALAYCAY J, MUMFORD RA, SWIDEREK KM, LEE TD, NATHAN C |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 176 Issue: 2 Pages: 599-604 Published: AUG 1 1992 |
| Times Cited: 492 References: 31 |
| Abstract: A central issue in nitric oxide (NO) research is to understand how NO can act in some settings as a servoregulator and in others as a cytotoxin. To answer this, we have sought a molecular basis for the differential regulation of the two known types of NO synthase (NOS). Constitutive NOS's in endothelium and neurons are activated by agonist-induced elevation of Ca2+ and resultant binding of calmodulin (CaM). In contrast, NOS in macrophages does not require added Ca2+ or CaM, but is regulated instead by transcription. We show here that macrophage NOS contains, as a tightly bound subunit, a molecule with the immunologic reactivity, high performance liquid chromatography retention time, tryptic map, partial amino acid sequence, and exact molecular mass of CaM. In contrast to most CaM-dependent enzymes, macrophage NOS binds CaM tightly without a requirement for elevated Ca2+. This may explain why NOS that is independent of Ca 2+ and elevated CaM appears to be activated simply by being synthesized. |
| Document Type: Note |
| Language: English |
Addresses:
1. CORNELL UNIV, MED CTR,COLL MED,DEPT MED,DIV HEMATOL ONCOL, BEATRICE & SAMUEL A SEAVER LAB, NEW YORK, NY 10021 USA
2. MERCK SHARP & DOHME LTD, DEPT BIOCHEM & MOLEC PATHOL, RAHWAY, NJ 07065 USA
3. CITY HOPE NATL MED CTR, BECKMAN RES INT, DIV IMMUNOL, DUARTE, CA 91010 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: JF803 |
| ISSN: 0022-1007 |
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