ATP2B4 binds to NOS1, inhibiting it

Stable Identifier
Reaction [binding]
Homo sapiens
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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

Oceandy, D, Cartwright, EJ, Baudoin, FM, Nadif, R, Pickard, A, Neyses, L, Hegab, Z, Alatwi, N, Zaki, AO, Mohamed, TM, Prehar, S

J. Biol. Chem. 2009
23549614 Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through calcium-induced dynamic interaction with neuronal nitric oxide synthase

Zhou, T, Duan, W, Li, W, Wei, T, Zhou, J, Yang, F, Chen, Q

Protein Cell 2013
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