@article {26613,
	title = {Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function},
	journal = {J Mol BiolJ Mol BiolJ Mol Biol},
	volume = {367},
	number = {1},
	year = {2007},
	note = {Vafiadaki, ElizabethSanoudou, DespinaArvanitis, Demetrios ACatino, Dawn HKranias, Evangelia GKontrogianni-Konstantopoulos, AikateriniengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2007/01/24 09:00J Mol Biol. 2007 Mar 16;367(1):65-79. doi: 10.1016/j.jmb.2006.10.057. Epub 2006 Oct 21.},
	month = {Mar 16},
	pages = {65-79},
	abstract = {Phospholamban (PLN) is a key regulator of Ca(2+) homeostasis and contractility in the heart. Its regulatory effects are mediated through its interaction with the sarcoplasmic reticulum Ca(2+)-ATPase, (SERCA2a), resulting in alterations of its Ca(2+)-affinity. To identify additional proteins that may interact with PLN, we used the yeast-two-hybrid system to screen an adult human cardiac cDNA library. HS-1 associated protein X-1 (HAX-1) was identified as a PLN-binding partner. The minimal binding regions were mapped to amino acid residues 203-245 for HAX-1 and residues 16-22 for PLN. The interaction between the two proteins was confirmed using GST-HAX-1, bound to the glutathione-matrix, which specifically adsorbed native PLN from human or mouse cardiac homogenates, while in reciprocal binding studies, recombinant His-HAX-1 bound GST-PLN. Kinetic studies using surface plasmon resonance yielded a K(D) of approximately 1 muM as the binding affinity for the PLN/HAX-1 complex. Phosphorylation of PLN by cAMP-dependent protein kinase reduced binding to HAX-1, while increasing concentrations of Ca(2+) diminished the PLN/HAX-1 interaction in a dose-dependent manner. HAX-1 concentrated to mitochondria, but upon transient co-transfection of HEK 293 cells with PLN, HAX-1 redistributed and co-localized with PLN at the endoplasmic reticulum. Analysis of the anti-apoptotic function of HAX-1 revealed that the presence of PLN enhanced the HAX-1 protective effects from hypoxia/reoxygenation-induced cell death. These findings suggest a possible link between the Ca(2+) handling by the sarcoplasmic reticulum and cell survival mediated by the PLN/HAX-1 interaction.},
	keywords = {Adaptor Proteins, Signal Transducing, Adult, Animals, Apoptosis/*drug effects, Calcium-Binding Proteins/*pharmacology, Humans, Mitochondrial Proteins/*metabolism/physiology, Myocardium/metabolism/*pathology, Phosphorylation, Proteins/*metabolism},
	isbn = {0022-2836 (Print)0022-2836 (Linking)},
	author = {Vafiadaki, E. and Sanoudou, D. and Arvanitis, DA and Catino, D. H. and Kranias, EG and Kontrogianni-Konstantopoulos, A.}
}
