The interaction between endogenous calcineurin and the plasma membrane calcium-dependent ATPase is isoform specific in breast cancer cells.
Plasma membrane calcium/calmodulin-dependent ATPases (PMCAs) are high affinity calcium pumps that extrude calcium from the cell. Emerging evidence suggests a novel role for PMCAs as regulators of calcium/calmodulin-dependent signal transduction pathways via interaction with specific partner proteins. In this work, we demonstrate that endogenous human PMCA2 and -4 both interact with the signal transduction phosphatase, calcineurin, whereas, no interaction was detected with PMCA1. The strongest interaction was observed between PMCA2 and calcineurin. The domain of PMCA2 involved in the interaction is equivalent to that reported for PMCA4b. PMCA2-calcineurin interaction results in inhibition of the calcineurin/nuclear factor of activated T-cells signalling pathway.
Holton
Marylouisa
M
Molecular Pharmacology Group, Research Institute in Healthcare Sciences, School of Applied Sciences, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1SB, UK.
Yang
Di
D
Wang
Weiguang
W
Mohamed
Tamer M A
TM
Neyses
Ludwig
L
Armesilla
Angel L
AL
D001943:Breast Neoplasms / Q000201:enzymology*; D019703:Calcineurin / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D002147:Calmodulin; D007527:Isoenzymes; D050778:NFATC Transcription Factors; D009363:Neoplasm Proteins; D019703:Calcineurin; D053499:Plasma Membrane Calcium-Transporting ATPases