Matches in SemOpenAlex for { <https://semopenalex.org/work/W3095696093> ?p ?o ?g. }
- W3095696093 endingPage "4237" @default.
- W3095696093 startingPage "4225" @default.
- W3095696093 abstract "Cationic amino acid transporters (CATs) supply cells with essential and semiessential dibasic amino acids. Among them, l-arginine is the substrate for nitric oxide synthases (NOS) to produce nitric oxide (NO), a key signaling molecule and second messenger. In cardiac preparations, we showed that NO acutely and directly modulates transport activity by noncompetitively inhibiting these CATs. We hypothesize that this NO regulation occurs through modification of cysteine residues in CAT proteins. Homology modeling and a computational chemistry approach identified Cys347 as one of two putative targets for NO binding, of 15 Cys residues present in the low-affinity mouse CAT-2A (mCAT-2A). To test this prediction, mammalian cell lines overexpressing mCAT-2A were used for site-directed mutagenesis and uptake studies. When Cys347 was replaced with alanine (Cys347Ala), mCAT-2A became insensitive to inhibition by NO donors. In addition, the transport capacity of this variant decreased by >50% compared to that of the control, without affecting membrane expression levels or apparent affinities for the transported amino acids. Interestingly, replacing Cys347 with serine (Cys347Ser) restored uptake levels to those of the control while retaining NO insensitivity. Other Cys residues, when replaced with Ala, still produced a NO-sensitive CAT-2A. In cells co-expressing NOS and mCAT-2A, exposure to extracellular l-arginine inhibited the uptake activity of control mCAT-2A, via NO production, but not that of the Cys347Ser variant. Thus, the -SH moiety of Cys347 is largely responsible for mCAT-2A inhibition by NO. Because of the endogenous NO effect, this modulation is likely to be physiologically relevant and a potential intervention point for therapeutics." @default.
- W3095696093 created "2020-11-09" @default.
- W3095696093 creator A5005264221 @default.
- W3095696093 creator A5023347989 @default.
- W3095696093 creator A5050161114 @default.
- W3095696093 creator A5069845765 @default.
- W3095696093 date "2020-11-02" @default.
- W3095696093 modified "2023-10-16" @default.
- W3095696093 title "Molecular Determinants for Nitric Oxide Regulation of the Murine Cationic Amino Acid Transporter CAT-2A" @default.
- W3095696093 cites W1519147845 @default.
- W3095696093 cites W15192671 @default.
- W3095696093 cites W1521256352 @default.
- W3095696093 cites W1524832496 @default.
- W3095696093 cites W1530740081 @default.
- W3095696093 cites W1596955265 @default.
- W3095696093 cites W1764308599 @default.
- W3095696093 cites W1927805387 @default.
- W3095696093 cites W1965932123 @default.
- W3095696093 cites W1969996414 @default.
- W3095696093 cites W1980812782 @default.
- W3095696093 cites W1989268736 @default.
- W3095696093 cites W1997023449 @default.
- W3095696093 cites W2004343006 @default.
- W3095696093 cites W2004494212 @default.
- W3095696093 cites W2004724154 @default.
- W3095696093 cites W2018745521 @default.
- W3095696093 cites W2025743226 @default.
- W3095696093 cites W2029667189 @default.
- W3095696093 cites W2031533866 @default.
- W3095696093 cites W2036923857 @default.
- W3095696093 cites W2037854429 @default.
- W3095696093 cites W2039870229 @default.
- W3095696093 cites W2044079355 @default.
- W3095696093 cites W2046123039 @default.
- W3095696093 cites W2055043387 @default.
- W3095696093 cites W2063089997 @default.
- W3095696093 cites W2064619021 @default.
- W3095696093 cites W2066601649 @default.
- W3095696093 cites W2067215588 @default.
- W3095696093 cites W2076644904 @default.
- W3095696093 cites W2081912151 @default.
- W3095696093 cites W2085094809 @default.
- W3095696093 cites W2087781182 @default.
- W3095696093 cites W2093278154 @default.
- W3095696093 cites W2101457798 @default.
- W3095696093 cites W2113336835 @default.
- W3095696093 cites W2135874673 @default.
- W3095696093 cites W2145806440 @default.
- W3095696093 cites W2156537912 @default.
- W3095696093 cites W2158123381 @default.
- W3095696093 cites W2158375208 @default.
- W3095696093 cites W2163559759 @default.
- W3095696093 cites W2164572096 @default.
- W3095696093 cites W2170220747 @default.
- W3095696093 cites W2179702494 @default.
- W3095696093 cites W2324058848 @default.
- W3095696093 cites W2558356717 @default.
- W3095696093 cites W2786180981 @default.
- W3095696093 cites W2989052455 @default.
- W3095696093 cites W3003543155 @default.
- W3095696093 cites W4211196614 @default.
- W3095696093 cites W4233734352 @default.
- W3095696093 doi "https://doi.org/10.1021/acs.biochem.0c00729" @default.
- W3095696093 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33135877" @default.
- W3095696093 hasPublicationYear "2020" @default.
- W3095696093 type Work @default.
- W3095696093 sameAs 3095696093 @default.
- W3095696093 citedByCount "1" @default.
- W3095696093 countsByYear W30956960932021 @default.
- W3095696093 crossrefType "journal-article" @default.
- W3095696093 hasAuthorship W3095696093A5005264221 @default.
- W3095696093 hasAuthorship W3095696093A5023347989 @default.
- W3095696093 hasAuthorship W3095696093A5050161114 @default.
- W3095696093 hasAuthorship W3095696093A5069845765 @default.
- W3095696093 hasConcept C104317684 @default.
- W3095696093 hasConcept C149011108 @default.
- W3095696093 hasConcept C178790620 @default.
- W3095696093 hasConcept C183882617 @default.
- W3095696093 hasConcept C185592680 @default.
- W3095696093 hasConcept C2778504605 @default.
- W3095696093 hasConcept C2781313199 @default.
- W3095696093 hasConcept C515207424 @default.
- W3095696093 hasConcept C519581460 @default.
- W3095696093 hasConcept C55493867 @default.
- W3095696093 hasConceptScore W3095696093C104317684 @default.
- W3095696093 hasConceptScore W3095696093C149011108 @default.
- W3095696093 hasConceptScore W3095696093C178790620 @default.
- W3095696093 hasConceptScore W3095696093C183882617 @default.
- W3095696093 hasConceptScore W3095696093C185592680 @default.
- W3095696093 hasConceptScore W3095696093C2778504605 @default.
- W3095696093 hasConceptScore W3095696093C2781313199 @default.
- W3095696093 hasConceptScore W3095696093C515207424 @default.
- W3095696093 hasConceptScore W3095696093C519581460 @default.
- W3095696093 hasConceptScore W3095696093C55493867 @default.
- W3095696093 hasFunder F4320337338 @default.
- W3095696093 hasIssue "44" @default.
- W3095696093 hasLocation W30956960931 @default.
- W3095696093 hasOpenAccess W3095696093 @default.