Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways

Table 1 Functional interactions between PMCA and calcium-dependent partner proteins

Protein partner	Domain of PMCA implicated in the interaction	Domain of partner protein implicated in the interaction	Functional consequence of the interaction	Proposed mechanism of regulation
nNOS, NOS-1	C-terminal PDZ-binding domain	PDZ domain	Decrease nNOS activity, decrease NO production	PMCA interactions tethers partner protein to a low calcium micro-environment, this results in inhibition of the enzymatic activity of the partner proteins
CASK	C-terminal PDZ-binding domain	PDZ domain	Decrease in T-element- dependent transcriptional activit	PMCA interactions tethers partner protein to a low calcium micro-environment, the complex CASK/Tbr-1 cannot be established
eNOS, NOS-3	Proximal region of the big, catalytic intracellular loop located between transmembrane domains 4 and 5 (amino acids 462-684 and 428-651 of PMCA2 and 4, respectively)	Region 735-934 of eNOS	Decrease eNOS activity, decrease NO production	PMCA interactions tethers partner protein to a low calcium micro-environment, this results in inhibition of the enzymatic activity of the partner proteins
Calcineurin A	Proximal region of the big, catalytic intracellular loop located between transmembrane domains 4 and 5 (amino acids 462-684 and 428-651 of PMCA2 and 4, respectively)	Region 58-143 of calcineurin A	Decrease in calcineurin/NFAT-dependent transcriptional activity	PMCA interactions tethers partner protein to a low calcium micro-environment, this results in inhibition of the enzymatic activity of the partner proteins

PMCA: Plasma membrane calcium ATPase; NOS: Nitric oxide synthase; nNOS: Neuronal NOS; eNOS: Endothelial NOS; CASK: Calmodulin-dependent serine protein kinase.