Disease relevance of ATP2B1

• Expression of plasma membrane calcium pump isoform mRNAs in breast cancer cell lines [1].
• In this study, we examined the regulation of PMCA expression during differentiation of the human neuroblastoma cell line IMR-32 [2].
• The identification of mice carrying PMCA mutations that lead to diseases such as hearing loss and ataxia, as well as the corresponding phenotypes of genetically engineered PMCA "knockout" mice further support the concept of specific, nonredundant roles for each Ca(2+) pump isoform in cellular Ca(2+) regulation [3].
• PMCA isoforms 4CII (generated by splicing at the C-terminus) and 4BICI (a pump version lacking the 10th transmembrane domain) were expressed in Sf9 cells using the baculovirus system [4].
• Transient forebrain ischemia (10 min) and reperfusion (for a prolonged period up to 10 d) leads to a significant decrease of PMCA immuno-signal [5].

Psychiatry related information on ATP2B1

• This review summarizes the results of recent analysis of the PMCA dysregulation in diseased cells or model systems of pathological conditions, including both acute disorders like hypoxia/ischemia and seizure, and slowly progressing dysfunctions like Alzheimer's disease, hypertension, diabetes and aging [6].

High impact information on ATP2B1

• During mouse embryonic development, PMCA1 is ubiquitously detected from the earliest time points, and all isoforms show spatially overlapping but distinct expression patterns with dynamic temporal changes occurring during late fetal development [3].
• The PMCA concept has been proved on the amplification of prions implicated in the pathogenesis of transmissible spongiform encephalopathies [7].
• Immunofluorescence experiments demonstrated an asymmetric localization of plasma membrane Ca(2+) ATPase (PMCA), which appeared to be partially co-localized with CaR and the gastric H(+)/K(+)-ATPase in the apical membrane of the acid-secreting cells [8].
• Here we demonstrate that PMCA 4b is a negative regulator of nitric oxide synthase I (NOS-I, nNOS) in HEK293 embryonic kidney and neuro-2a neuroblastoma cell models [9].
• Effects of PMCA and SERCA pump overexpression on the kinetics of cell Ca(2+) signalling [10].

Chemical compound and disease context of ATP2B1

• Our results suggest that PMCA expression may be altered in breast cancer cell lines, suggesting altered Ca(2+) regulation in these cell lines [1].
• The aim of the study was to estimate PMCA (plasma membrane Ca-transporting adenosine triphosphatase; ATPase 3.6.1.38) activity and calcium homeostasis in erythrocytes of children with chronic kidney disease (CKD) [11].

Biological context of ATP2B1

• Alternative splicing was found to occur in the PMCA transcripts at two major regulatory sites (sites A and C), adjacent to the amino-terminal phospholipid-responsive region and within the carboxyl-terminal calmodulin binding domain, respectively [12].
• In accordance with the ubiquitous tissue distribution of its mRNA these results suggest that the hPMCA1 gene is of the housekeeping type [13].
• The plasma membrane Ca(2+) ATPase (PMCA) is an important regulator of free intracellular calcium, with dynamic regulation in the rat mammary gland during lactation [1].
• Considering the harmful effects of increased intracellular calcium levels, the upregulation of both SERCA and PMCA pumps suggests it is a compensatory mechanism to restore the calcium concentration to the physiological resting level [14].
• Isoforms of the plasma membrane Ca(2+)-ATPase (PMCA) and SERCA were quantified by Western blot and quantitative real time reverse transcription polymerase chain reaction [14].

Anatomical context of ATP2B1

• Human plasma membrane Ca2(+)-ATPase (PMCA) isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts [15].
• We found that the relative expression of PMCA1 mRNA is increased, by approximately 270% and 170%, in MCF-7 and MDA-MB-231 human breast cancer cell lines deprived of serum for 72 h, respectively, compared to the similarly treated MCF-10A human mammary gland epithelial cell line [1].
• In contrast to PMCA4, PMCA1 immunoreactivity (IR) was located on portions of basal cell plasma membranes adjacent to the stroma [16].
• We have found that PMCA1 and PMCA4 genes were expressed in 8-, 12- and 20-week fetal heart and in adult heart [17].
• We cloned and sequenced eight cDNA inserts encoding for the PMCA1 and PMCA4 variants from a fetal human heart cDNA library confirming that these are the two main PMCA genes expressed in cardiac muscle [17].

Associations of ATP2B1 with chemical compounds

• We showed that both PMCA1 and SERCA3 isoform protein and mRNA are upregulated two- to three-fold in thapsigargin-treated HLE B-3 cells in a time and dose-dependent manner [14].
• Plasma membrane Ca(2+)-ATPases (PMCAs) are involved in local Ca(2+) signaling and in the spatial control of Ca(2+) extrusion, but how different PMCA isoforms are targeted to specific membrane domains is unknown [18].
• A 1.4-fold- and 2.0-fold-higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively [19].
• PMCA associates much more strongly with phosphatidylcholine containing disordered hydrocarbon chains than ordered hydrocarbon chains [20].
• These findings suggest a role for phosphoinositide 3-kinase in regulating PMCA expression, which may be important in the control of Ca(2+)-sensitive VSMC functions [21].

Regulatory relationships of ATP2B1

• Expression of other isoforms such as PMCA4 may influence mammary gland epithelial cell proliferation and aberrant regulation of PMCA isoform expression may lead or contribute to mammary gland pathophysiology in the form of breast cancers [22].

Other interactions of ATP2B1

• Novel splicing variants not described previously for human genes were detected for hPMCA3 and 4 at site A and for hPMCA1, 2, and 3 at site C [12].
• Characterization of PMCA mRNA isoforms revealed that PMCA1b and PMCA4 mRNA are expressed in MCF-7, MDA-MB-231, SK-BR-3, ZR-75-1 and BT-483 breast cancer cell lines [1].
• The recombinant PMCA1 pump was a much better substrate for the cAMP-dependent protein kinase than the PMCA2 and PMCA4 isoforms [23].
• Using an RT-PCR approach, expression of the epithelial calcium channel (CaT-Like), the calcium binding protein (calbindin-2), the endoplasmic reticulum pumps (SERCA-2 and -3), and the plasma membrane calcium ATPases (PMCA-1, -2, and -4), were found in parotid and submandibular glands [24].
• The plasma membrane Ca(2+)-pumping ATPase (Ca(2+)-ATPase) mRNAs are encoded on four different genes designated PMCA1-PMCA4 [25].

Analytical, diagnostic and therapeutic context of ATP2B1

• METHODS: PMCA mRNA expression was examined by RT-PCR analysis of total RNA from native hCE using PMCA gene specific primers [16].
• PMCA isoform expression at the protein level in native hCE was examined by immunoblotting using isoform specific antibodies (Abs) and a panPMCA Ab that recognizes all PMCAs [16].
• Specific probes detect major mRNA species of 5.6 kilobases for hPMCA1, and of 7.5 kilobases for hPMCA3, on Northern blots of human K562 erythroleukemic cell RNA [26].
• In situ hybridization was employed to determine the expression pattern of the four human PMCA isoforms in the human hippocampus [27].
• PURPOSE: To compare the effect of 20 cm SDS-PAGE electrophoresis, which is most widely used in proteomic research, in identifying human lens epithelium B3 (HLE B3) cells plasma membrane calcium ATPase (PMCA) isoform's apparent molecular weight (MW), with that of 8 cm SDS-PAGE electrophoresis [28].

References