Protein Kinase A Phosphorylates Titin’s Cardiac-Specific N2B Domain and Reduces Passive Tension in Rat Cardiac Myocytes
作者:
R. Yamasaki,
Y. Wu,
M. McNabb,
M. Greaser,
S. Labeit,
H. Granzier,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 90,
issue 11
页码: 1181-1188
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: connectin;diastole;myocyte mechanics;&bgr;-adrenergic signaling;resting tension
数据来源: OVID
摘要:
&bgr;-Adrenergic stimulation of cardiac muscle activates protein kinase A (PKA), which is known to phosphorylate proteins on the thin and thick filaments of the sarcomere. Cardiac muscle sarcomeres contain a third filament system composed of titin, and here we demonstrate that titin is also phosphorylated by the &bgr;-adrenergic pathway. Titin phosphorylation was observed after &bgr;-receptor stimulation of intact cardiac myocytes and incubation of skinned cardiac myocytes with PKA. Mechanical experiments with isolated myocytes revealed that PKA significantly reduces passive tension. In vitro phosphorylation of recombinant titin fragments and immunoelectron microscopy suggest that PKA targets a subdomain of the elastic segment of titin, referred to as the N2B spring element. The N2B spring element is expressed only in cardiac titins, in which it plays an important role in determining the level of passive tension. Because titin-based passive tension is a determinant of diastolic function, these results suggest that titin phosphorylation may modulate cardiac function in vivo.
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