Kalirin inhibition of inducible nitric-oxide synthase.
Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity.
Ratovitski
E A
EA
Division of Cardiology, School of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Alam
M R
MR
Quick
R A
RA
McMillan
A
A
Bao
C
C
Kozlovsky
C
C
Hand
T A
TA
Johnson
R C
RC
Mains
R E
RE
Eipper
B A
BA
Lowenstein
C J
CJ
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D002460:Cell Line; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D020662:Guanine Nucleotide Exchange Factors; C102365:Kalrn protein, rat; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019204:GTP-Binding Proteins