FK506 Blocks Intracellular Ca<sup>2+</sup> Oscillations in Bovine Adrenal Glomerulosa Cells

Sn, Poirier; Poitras, Marc F.; Chorvatova, Alzbeta; Payet,; Guillemette, Gaétan

doi:10.1021/bi010207k

Cited by 25 publications

(21 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In nuclei isolated from rat liver (unknown composition of IP 3 R/channel), PKC enhanced IP 3 -induced Ca 2C release (Matter et al 1993). In bovine adrenal glomerulosa cells, which express all three subtypes of IP 3 R (but a large majority of IP 3 R-1), PKC enhanced IP 3 -induced Ca 2C release (Poirier et al 2001). In rat brain microsomes, a tissue containing exclusively the IP 3 R-1 subtype, PKC also increased IP 3 -induced Ca 2C release (Cameron et al 1995).…”

Section: Discussionmentioning

confidence: 96%

“…We also demonstrated that endogenous PKC phosphorylates IP 3 R-2 in intact AR4-2J cells. Previous studies demonstrated that IP 3 Rs are a substrate for PKC but these studies were done with cells or tissues expressing exclusively the IP 3 R-1 subtype (Cameron et al 1995), or a mixture of all three IP 3 R subtypes (Matter et al 1993, Poirier et al 2001. A recent study reported that full-length mouse IP 3 R-1 and full-length rat IP 3 R-3 expressed in Sf9 insect cells are good substrates for PKC (Vermassen et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies showed that PKC increases IP 3 -induced Ca 2C release in tissues expressing in large majority the subtype IP 3 R-1 (Matter et al 1993, Poirier et al 2001), but little is known about the effect of PKC on IP 3 R-2 and IP 3 R-3. The rat pancreatoma cell line AR4-2J expresses IP 3 R-2 almost exclusively and thus constitutes a good model for the study of this particular IP 3 R subtype.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Protein kinase C phosphorylates the inositol 1,4,5-trisphosphate receptor type 2 and decreases the mobilization of Ca2+in pancreatoma AR4-2J cells

Arguin

Regimbald-Dumas

Frégeau

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

In non-excitable cells, the inositol 1,4,5-trisphosphate receptor (IP 3 R) is an intracellular Ca 2C channel, which plays a major role in Ca 2C signalling. Three isoforms of IP 3 R have been identified (IP 3 R-1, IP 3 R-2 and IP 3 R-3) and most cell types express different proportions of each isoform. The differences between the pharmacological and functional properties of the various isoforms of IP 3 R are poorly understood. AR4-2J cells, which express almost exclusively (w86%) the IP 3 R-2, represent an interesting model to study this particular isoform. Here, we investigated a regulatory mechanism by which protein kinase C (PKC) influences IP 3 R-2-mediated Ca 2C release. Using an immunoprecipitation approach, we confirmed that AR4-2J cells express almost exclusively the IP 3 R-2 isoform. Using an in vitro phosphorylation assay, we showed that the immunopurified IP 3 R-2 was efficiently phosphorylated by exogenous PKC. In intact AR4-2J cells metabolically labelled with 32 Pi, we showed that phorbol-12-myristate-13-acetate (PMA) and Ca 2C mobilizing agonists cause the phosphorylation of IP 3 R-2. In saponin-permeabilized AR4-2J cells, IP 3 -induced Ca 2C release was reduced after a pre-treatment with PMA or with exogenous PKC. PMA also reduced the Ca 2C response of intact AR4-2J cells stimulated with carbachol and epidermal growth factor, two agonists that use different receptor types to activate phospholipase C. These results demonstrate that PKC decreases the Ca 2C mobilizing activity of IP 3 R-2 and thus exerts a negative feedback on the agonists-induced Ca 2C response of AR4-2J cells.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protein kinase C phosphorylates the inositol 1,4,5-trisphosphate receptor type 2 and decreases the mobilization of Ca2+in pancreatoma AR4-2J cells

Arguin

Regimbald-Dumas

Frégeau

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…It has been described that mTOR may stimulate phosphorylation of 4E-BP1 indirectly by inactivating some phosphatases (PP2A, PP4, PP6) that would lead to the phosphorylation of 4E-BP1 (47), but it is not known how PP2A or these other phosphatases are regulated. It has also been described that 4E-BP1 phosphorylation can be dependent on calcium and calmodulin activation, independently of the PI3K/Akt/mTOR pathway activation (47) (43). However, the lack of a strong effect on amylase secretion makes this mechanism unlikely.…”

Section: Discussionmentioning

confidence: 99%

Calcineurin is required for translational control of protein synthesis in rat pancreatic acini

Sans¹,

Williams²

2004

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Sans, Maria Dolors, and John A. Williams. Calcineurin is required for translational control of protein synthesis in rat pancreatic acini. Am J Physiol Cell Physiol 287: C310 -C319, 2004. First published March 24, 2004 10.1152 10. /ajpcell.00534.2003creases the rate of net protein synthesis in rat pancreatic acini by activating initiation and elongation factors required for translation. The immunosuppressant FK506 inhibits the Ca 2ϩ -calmodulin-dependent phosphatase calcineurin in pancreatic acinar cells and blocks pancreatic growth induced by chronic CCK treatment. To test a requirement for calcineurin in the activation of the translational machinery stimulated by CCK, we evaluated the effects of FK506 on protein synthesis and on regulatory initiation and elongation factors in rat pancreatic acini in vitro. CCK acutely increased protein synthesis in acini from normal rats with a maximum increase at 100 pM CCK to 170 Ϯ 11% of control. The immunosuppressant FK506 dosedependently inhibited CCK-stimulated protein synthesis over the same concentration range that blocked calcineurin activity, as assessed by dephosphorylation of the calcineurin substrate calciumregulated heat-stable protein of 24 kDa. Another immunosuppressant, cyclosporin A, inhibited protein synthesis, but its effects appeared more complex. FK506 also inhibited protein synthesis stimulated by bombesin and carbachol. FK506 did not significantly affect the activity of the initiation factor-2B, or the phosphorylation of the initiation factor-2␣, ribosomal protein protein S6, or the mRNA cap binding protein eukaryotic initiation factor (eIF) 4E. Instead, blockade of calcineurin with FK506 reduced the phosphorylation of the eIF4E binding protein, reduced the formation of the eIF4F complex, and increased the phosphorylation of eukaryotic elongation factor 2. From these results, we conclude that calcineurin activity is required for protein synthesis, and this action may be related to an effect on the formation of the mRNA cap binding complex and the elongation processes. exocrine pancreas; cholecystokinin; translation initiation factors; protein phosphatase 2B; immunosuppressants CALCINEURIN, ALSO KNOWN AS protein phosphatase 2B (PP2B), is a serine/threonine protein phosphatase (48) that is highly regulated by Ca 2ϩ

show abstract

“…This association increases IP 3 R phosphorylation and enhances Ca 2+ release (Cameron et al, 1995a). Again, in adrenal glomerulosa cells, both Ca 2+ signalling and protein kinase C (PKC)-mediated phosphorylation of the IP 3 R were modified by FK506 (Poirier et al, 2001), whereas in COS-7 cells, calcineurin reduced IP 3 -induced Ca 2+ release, an effect reversed by FK506 (Bandyopadhyay et al, 2000). However, as with FKBP12, the mechanisms by which calcineurin regulates Ca 2+ release from IP 3 R are disputed.…”

mentioning

confidence: 99%

In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin

MacMillan

Currie

Bradley

et al. 2005

Journal of Cell Science

View full text Add to dashboard Cite

Ca2+ release from the sarcoplasmic reticulum (SR) by the IP3 receptors (IP3Rs) crucially regulates diverse cell signalling processes from reproduction to apoptosis. Release from the IP3R may be modulated by endogenous proteins associated with the receptor, such as the 12 kDa FK506-binding protein (FKBP12), either directly or indirectly by inhibition of the phosphatase calcineurin. Here, we report that, in addition to calcineurin, FKPBs modulate release through the mammalian target of rapamycin (mTOR), a kinase that potentiates Ca2+ release from the IP3R in smooth muscle. The presence of FKBP12 was confirmed in colonic myocytes and co-immunoprecipitated with the IP3R. In aortic smooth muscle, however, although present, FKBP12 did not co-immunoprecipitate with IP3R. In voltage-clamped single colonic myocytes rapamycin, which together with FKBP12 inhibits mTOR (but not calcineurin), decreased the rise in cytosolic Ca2+ concentration ([Ca2+]c) evoked by IP3R activation (by photolysis of caged IP3), without decreasing the SR luminal Ca2+ concentration ([Ca2+]l) as did the mTOR inhibitors RAD001 and LY294002. However, FK506, which with FKBP12 inhibits calcineurin (but not mTOR), potentiated the IP3-evoked [Ca2+]c increase. This potentiation was due to the inhibition of calcineurin; it was mimicked by the phosphatase inhibitors cypermethrin and okadaic acid. The latter two inhibitors also prevented the FK506-evoked increase as did a calcineurin inhibitory peptide (CiP). In aortic smooth muscle, where FKBP12 was not associated with IP3R, the IP3-mediated Ca2+ release was unaffected by FK506 or rapamycin. Together, these results suggest that FKBP12 has little direct effect on IP3-mediated Ca2+ release, even though it is associated with IP3R in colonic myocytes. However, FKBP12 might indirectly modulate Ca2+ release through two effector proteins: (1) mTOR, which potentiates and (2) calcineurin, which inhibits Ca2+ release from IP3R in smooth muscle

show abstract

FK506 Blocks Intracellular Ca²⁺ Oscillations in Bovine Adrenal Glomerulosa Cells

Cited by 25 publications

References 43 publications

Protein kinase C phosphorylates the inositol 1,4,5-trisphosphate receptor type 2 and decreases the mobilization of Ca2+in pancreatoma AR4-2J cells

Protein kinase C phosphorylates the inositol 1,4,5-trisphosphate receptor type 2 and decreases the mobilization of Ca2+in pancreatoma AR4-2J cells

Calcineurin is required for translational control of protein synthesis in rat pancreatic acini

In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin

Contact Info

Product

Resources

About

FK506 Blocks Intracellular Ca2+ Oscillations in Bovine Adrenal Glomerulosa Cells

Cited by 25 publications

References 43 publications

Protein kinase C phosphorylates the inositol 1,4,5-trisphosphate receptor type 2 and decreases the mobilization of Ca2+in pancreatoma AR4-2J cells

Protein kinase C phosphorylates the inositol 1,4,5-trisphosphate receptor type 2 and decreases the mobilization of Ca2+in pancreatoma AR4-2J cells

Calcineurin is required for translational control of protein synthesis in rat pancreatic acini

In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin

Contact Info

Product

Resources

About

FK506 Blocks Intracellular Ca²⁺ Oscillations in Bovine Adrenal Glomerulosa Cells