Troponin I chimera analysis of the cardiac myofilament tension response to protein kinase A

American Journal of Physiology - Cell Physiology - Tập 280 Số 2 - Trang C324-C332 - 2001
Margaret V. Westfall1, Immanuel I. Turner1, Faris Albayya1, Joseph M. Metzger1
1Department of Physiology, School of Medicine, University of Michigan, Ann Arbor, Michigan 48109-0622

Tóm tắt

Viral-mediated gene transfer of troponin I (TnI) isoforms and chimeras into adult rat cardiac myocytes was used to investigate the role TnI domains play in the myofilament tension response to protein kinase A (PKA). In myocytes expressing endogenous cardiac TnI (cTnI), PKA phosphorylated TnI and myosin-binding protein C and decreased the Ca2+ sensitivity of myofilament tension. In marked contrast, PKA did not influence Ca2+-activated tension in myocytes expressing the slow skeletal isoform of TnI or a chimera (N-slow/card-C TnI), which lack the unique phosphorylatable amino terminal extension found in cTnI. PKA-mediated phosphorylation of a second TnI chimera, N-card/slow-C TnI, which has the amino terminal region of cTnI, caused a decrease in the Ca2+ sensitivity of tension comparable in magnitude to control myocytes. Based on these results, we propose the amino terminal region shared by cTnI and N-card/slow-C TnI plays a central role in determining the magnitude of the PKA-mediated shift in myofilament Ca2+ sensitivity, independent of the isoform-specific functional domains previously defined within the carboxyl terminal backbone of TnI. Interestingly, exposure of permeabilized myocytes to acidic pH after PKA-mediated phosphorylation of cTnI resulted in an additive decrease in myofilament Ca2+ sensitivity. The isoform-specific, pH-sensitive region within TnI lies in the carboxyl terminus of TnI, and the additive response provides further evidence for the presence of a separate domain that directly transduces the PKA phosphorylation signal.

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Tài liệu tham khảo

10.1111/j.1432-1033.1995.tb20347.x

Bartel S, 1989, Biomed Biochim Acta, 48, S108

10.1006/jmcc.1994.1131

10.1007/BF00227896

10.1161/01.CIR.96.5.1495

10.1021/bi9710129

10.1021/bi9622276

10.1016/0014-5793(75)81040-4

10.1016/0076-6879(88)57093-3

10.1096/fasebj.9.9.7601340

10.1111/j.1469-7793.1999.0143z.x

10.1074/jbc.274.24.16681

10.1016/0003-2697(83)90551-1

10.1085/jgp.80.2.279

10.1161/01.RES.74.4.718

10.1016/0304-4165(79)90405-7

10.1023/A:1005381131102

10.1016/0014-5793(80)80418-2

10.1016/S0021-9258(18)71681-5

10.1152/ajpheart.1997.272.1.H360

10.1021/bi00208a026

10.1152/ajpheart.1998.274.2.H385

10.1016/S0006-3495(95)80316-4

10.1016/0014-5793(90)81046-Q

10.1016/0014-5793(92)80423-E

10.1152/ajpcell.1996.270.1.C107

10.1021/bi00217a018

10.1152/ajpcell.1990.258.6.C967

10.1006/jmcc.1998.0854

10.1023/A:1006939307715

10.1016/0014-5793(95)00812-N

10.1074/jbc.272.43.26887

10.1111/j.1432-1033.1990.tb15612.x

10.1006/jmbi.1997.1200

10.1074/jbc.274.32.22508

10.1161/01.RES.86.4.470

10.1016/S0091-679X(08)60385-4

10.1073/pnas.94.10.5444

10.1002/(SICI)1097-0177(199605)206:1<24::AID-AJA3>3.0.CO;2-2

10.1152/ajpcell.1996.271.1.C391

10.1161/01.CIR.99.4.505

10.1161/01.RES.76.6.1028

10.1074/jbc.270.51.30773

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American Journal of Physiology - Cell Physiology

Tập 280 Số 2

C324-C332

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