Protein-protein interactions involving inducible nitric oxide synthase.
OBJECTIVE
Nitric oxide (NO) is a signaling and effector molecule that contributes to multiple physiological and pathophysiological processes in the kidney, vasculature, and other tissues. High output NO generation by inducible NO synthase (iNOS) participates in host defense against pathogens and contributes to tissue injury during inflammatory states. Because of its potent reactivity and diffusibility, NO generation by iNOS is subject to multiple levels of regulation, including transcriptional, translational, and post-translational controls, including protein-protein interactions. This review examines the experimental basis for these protein-protein interactions and their known and potential importance for kidney and vascular physiology.


METHODS
Analysis of the biomedical literature in the area.


RESULTS
iNOS interacts with the inhibitory molecules Kalirin and NOS-associated protein 1.10 kd (NAP110), which inhibit iNOS homodimerization, as well as activator proteins, the Rac-GTPases. Interactions with caveolin-1 control the intracellular locale and degradation of iNOS in tumor cells. In polarized epithelial cells, associations of iNOS with the scaffolding protein EBP50 position iNOS in the apical membrane near key ion transport proteins that also interact with EPB50. In addition, protein-protein interactions of proteins governing iNOS transcription function to specify activation or suppression of iNOS induction by cytokines.


CONCLUSIONS
Interactions of iNOS with a diverse group of heterologous proteins provides a selective mechanism to control the activity, spatial distribution, and proximity of iNOS to intended targets, while potentially limiting autotoxicity to the iNOS-expressing cell.
D001798:Blood Proteins / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D000099149:Ezrin
D001798:Blood Proteins; D002147:Calmodulin; D002352:Carrier Proteins; D051242:Caveolin 1; D022461:Caveolins; D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D014157:Transcription Factors; D020744:rac GTP-Binding Proteins; D000099149:Ezrin; C495540:CAV1 protein, human; C102365:Kalrn protein, rat; C071058:moesin; C071776:radixin; C496319:NOS2 protein, human