Reactome | ATP2B4 binds to NOS1, inhibiting it

ATP2B4 binds to NOS1, inhibiting it

Stable Identifier

R-HSA-5617178

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Plasma membrane calcium-transporting ATPase 4 (ATP2B4 aka PMCA4) binds and inhibits cardiac neuronal nitric-oxide synthase (NOS1 aka nNOS, a powerful regulator of the beta-adrenergic contractile response in the heart) by changing local calcium concentration (Duan et al. 2013). Reduced nNOS activity leads to a reduction in cGMP which in turn results in the reduction of phosphodiesterase (PDE) activity. As a result, cAMP degradation is prevented, increasing protein kinase A (PKA) activity, which can lead to increased phosphorylation of proteins involved in the excitation-contraction coupling process such as cardiac phospholamban (PLN aka PLB) and of cardiac muscle troponin I (TNNI3 aka cTnI) (Mohamed et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
19278978	Specific role of neuronal nitric-oxide synthase when tethered to the plasma membrane calcium pump in regulating the beta-adrenergic signal in the myocardium Mohamed, TM, Oceandy, D, Prehar, S, Alatwi, N, Hegab, Z, Baudoin, FM, Pickard, A, Zaki, AO, Nadif, R, Cartwright, EJ, Neyses, L	J. Biol. Chem.	2009
23549614	Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through calcium-induced dynamic interaction with neuronal nitric oxide synthase Duan, W, Zhou, J, Li, W, Zhou, T, Chen, Q, Yang, F, Wei, T	Protein Cell	2013