PMID:12660151

Citation	Afroze, T, Yang, LL, Wang, C, Gros, R, Kalair, W, Hoque, AN, Mungrue, IN, Zhu, Z and Husain, M (2003) Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle. Am. J. Physiol., Cell Physiol. 285:C88-95
Abstract	Calcineurin mediates repression of plasma membrane Ca2+-ATPase-4 (PMCA4) expression in neurons, whereas c-Myb is known to repress PMCA1 expression in vascular smooth muscle cells (VSMC). Here, we describe a novel mouse VSMC line (MOVAS) in which 45Ca efflux rates decreased 50%, fura 2-AM-based intracellular Ca2+ concentrations ([Ca2+]i) increased twofold, and real-time RT-PCR and Western blot revealed a approximately 40% decrease in PMCA4 expression levels from G0 to G1/S in the cell cycle, where PMCA4 constituted approximately 20% of total PMCA protein. Although calcineurin activity increased fivefold as MOVAS progressed from G0 to G1/S, inhibition of this increase with either BAPTA or retroviral transduction with peptide inhibitors of calcineurin (CAIN), or its downstream target nuclear factor of activated T cells (NFAT) (VIVIT), had no effect on the repression of PMCA4 mRNA expression at G1/S. By contrast, Ca2+-independent activity of the calmodulin-dependent protein kinase-II (CaMK-II) increased eightfold as MOVAS progressed from G0 to G1/S, and treatment with an inhibitor of CaMK-II (KN-93) or transduction of a c-Myb-neutralizing antibody significantly alleviated the G1/S-associated repression of PMCA4. These data show that G1/S-specific PMCA4 repression in proliferating VSMC is brought about by c-Myb and CaMK-II and that calcineurin may regulate cell cycle-associated [Ca2+]i through alternate targets.
Links	PubMed Online version:10.1152/ajpcell.00518.2002
Keywords	Animals; Antibodies/pharmacology; Benzylamines/pharmacology; Calcineurin/antagonists & inhibitors; Calcineurin/metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Calcium-Transporting ATPases/genetics; Calcium-Transporting ATPases/metabolism; Carrier Proteins/genetics; Cation Transport Proteins; Cell Line; Cell Membrane/enzymology; Cell Size/physiology; Chelating Agents/pharmacology; Egtazic Acid/analogs & derivatives; Egtazic Acid/pharmacology; Enzyme Inhibitors/pharmacology; G1 Phase/physiology; Gene Expression Regulation, Enzymologic/physiology; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular/cytology; Muscle, Smooth, Vascular/enzymology; Oligopeptides/genetics; Phenotype; Plasma Membrane Calcium-Transporting ATPases; Proto-Oncogene Proteins c-myb/immunology; Proto-Oncogene Proteins c-myb/metabolism; S Phase/physiology; Sulfonamides/pharmacology; Transfection
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.