Role of calcineurin and protein phosphatase-2A in the regulation of phosphatase inhibitor-1 in cardiac myocytes.
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Role of calcineurin and protein phosphatase-2A in the regulation of phosphatase inhibitor-1 in cardiac myocytes. / El-Armouche, Ali; Bednorz, Anna; Pamminger, Torsten; Ditz, Diana; Didié, Michael; Dobrev, Dobromir; Eschenhagen, Thomas.
In: BIOCHEM BIOPH RES CO, Vol. 346, No. 3, 3, 2006, p. 700-706.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Role of calcineurin and protein phosphatase-2A in the regulation of phosphatase inhibitor-1 in cardiac myocytes.
AU - El-Armouche, Ali
AU - Bednorz, Anna
AU - Pamminger, Torsten
AU - Ditz, Diana
AU - Didié, Michael
AU - Dobrev, Dobromir
AU - Eschenhagen, Thomas
PY - 2006
Y1 - 2006
N2 - Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), the predominating Ser/Thr phosphatase in the heart. Non-phosphorylated I-1 is inactive, whereas I-1 phosphorylated by protein kinase A (PKA) at Thr35 is a potent PP1 inhibitor. The phosphatases that dephosphorylate I-1Thr35 and thus deactivate I-1 in the heart are not established. Here we overexpressed I-1 in neonatal rat cardiac myocytes with recombinant adenovirus and determined phosphorylation of I-1, and one of the major target proteins of PKA/PP1 in the heart, phospholamban (PLB), by Western blot with phospho-specific antibodies. Incubation with the calcineurin inhibitor cyclosporine A or okadaic acid, used at a concentration preferentially inhibiting phosphatase 2A (PP2A), increased significantly I-1Thr35 (approximately 2- to 6-fold) and PLB Ser16 phosphorylation (approximately 2-fold). The results indicate that calcineurin and PP2A act to maintain a low basal level of phosphorylated (active) I-1 in living cardiac myocytes. Calcineurin may constitute a cross-talk between calcium- and cAMP-dependent pathways.
AB - Inhibitor 1 (I-1) is a protein inhibitor of protein phosphatase 1 (PP1), the predominating Ser/Thr phosphatase in the heart. Non-phosphorylated I-1 is inactive, whereas I-1 phosphorylated by protein kinase A (PKA) at Thr35 is a potent PP1 inhibitor. The phosphatases that dephosphorylate I-1Thr35 and thus deactivate I-1 in the heart are not established. Here we overexpressed I-1 in neonatal rat cardiac myocytes with recombinant adenovirus and determined phosphorylation of I-1, and one of the major target proteins of PKA/PP1 in the heart, phospholamban (PLB), by Western blot with phospho-specific antibodies. Incubation with the calcineurin inhibitor cyclosporine A or okadaic acid, used at a concentration preferentially inhibiting phosphatase 2A (PP2A), increased significantly I-1Thr35 (approximately 2- to 6-fold) and PLB Ser16 phosphorylation (approximately 2-fold). The results indicate that calcineurin and PP2A act to maintain a low basal level of phosphorylated (active) I-1 in living cardiac myocytes. Calcineurin may constitute a cross-talk between calcium- and cAMP-dependent pathways.
M3 - SCORING: Zeitschriftenaufsatz
VL - 346
SP - 700
EP - 706
JO - BIOCHEM BIOPH RES CO
JF - BIOCHEM BIOPH RES CO
SN - 0006-291X
IS - 3
M1 - 3
ER -
