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 Ca2+ and elevated CaM appears to be activated simply by being synthesized.
Calmodulin is a subunit of nitric oxide synthase from macrophages.
H J Cho, Q W Xie, J Calaycay, R A Mumford, K M Swiderek, T D Lee, C Nathan; Calmodulin is a subunit of nitric oxide synthase from macrophages.. J Exp Med 1 August 1992; 176 (2): 599–604. doi: https://doi.org/10.1084/jem.176.2.599
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