Na+/K+‐ATPase as a signal transducer

FEBS Journal - Tập 269 Số 10 - Trang 2434-2439 - 2002
Zijian Xie1, Amir Askari1
1Department of Pharmacology, Medical College of Ohio, Toledo, USA

Tóm tắt

Na+/K+‐ATPase as an energy transducing ion pump has been studied extensively since its discovery in 1957. Although early findings suggested a role for Na+/K+‐ATPase in regulation of cell growth and expression of various genes, only in recent years the mechanisms through which this plasma membrane enzyme communicates with the nucleus have been studied. This research, carried out mostly on cardiac myocytes, shows that in addition to pumping ions, Na+/K+‐ATPase interacts with neighboring membrane proteins and organized cytosolic cascades of signaling proteins to send messages to the intracellular organelles. The signaling pathways that are rapidly elicited by the interaction of ouabain with Na+/K+‐ATPase, and are independent of changes in intracellular Na+ and K+ concentrations, include activation of Src kinase, transactivation of the epidermal growth factor receptor by Src, activation of Ras and p42/44 mitogen‐activated protein kinases, and increased generation of reactive oxygen species by mitochondria. In cardiac myocytes, the resulting downstream events include the induction of some early response proto‐oncogenes, activation of the transcription factors, activator protein‐1 and nuclear factor kappa‐B, regulation of a number of cardiac growth‐related genes, and stimulation of protein synthesis and myocyte hypertrophy. For these downstream events, the induced reactive oxygen species and rise in intracellular Ca2+ are essential second messengers. In cells other than cardiac myocytes, the proximal pathways linked to Na+/K+‐ATPase through protein–protein interactions are similar to those reported in myocytes, but the downstream events and consequences may be significantly different. The likely extracellular physiological stimuli for the signal transducing function of Na+/K+‐ATPase are the endogenous ouabain‐like hormones, and changes in extracellular K+ concentration.

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Tài liệu tham khảo

10.1016/0006-3002(57)90343-8

10.1152/physrev.1965.45.3.596

10.1046/j.1432-1033.2002.02909.x

10.1113/jphysiol.1974.sp010684

10.1007/BF01870996

Rayson B.M., 1993, Calcium: a mediator of the cellular response to chronic Na+/K+‐ATPase inhibition, J. Biol. Chem., 268, 8851, 10.1016/S0021-9258(18)52951-3

10.1172/JCI116781

10.1046/j.1471-4159.1997.69052189.x

10.1007/BF00233355

Nakagawa Y., 1992, A role for the Na/K‐ATPase in the control of human c‐fos and c‐jun transcription, J. Biol. Chem., 267, 8785, 10.1016/S0021-9258(19)50347-7

10.1016/0042-6822(92)91207-B

10.1016/0014-5793(95)01301-6

10.1161/01.CIR.96.5.1501

McGowan M.H., 1999, Na+,K+‐ATPase inhibitors down‐regulate gene expression of the intracellular signaling protein 14‐3‐3 in rat lens, J. Pharmacol. Exp. Ther., 289, 1559

10.1146/annurev.ph.40.030178.000315

10.1038/219198a0

10.1254/jjp.72.347

10.1016/0005-2736(81)90258-3

Szamel M., 1981, Functional interrelationship between (Na+ + K+)‐ATPase and lysolecithin acyltransferase in plasma membrane of mitogen‐stimulated rabbit thymocytes, J. Biol. Chem., 256, 9198, 10.1016/S0021-9258(19)52528-5

10.1002/jcp.1041650205

10.1006/jmcc.1997.0523

10.1074/jbc.271.17.10372

10.1006/jmcc.1996.0320

10.1006/jmcc.1997.0546

10.1074/jbc.273.24.15249

10.1074/jbc.274.27.19323

10.1161/01.RES.84.6.633

10.1016/0024-3205(76)90017-5

10.1074/jbc.M002951200

Liu J., 2000, Ouabain interaction with cardiac Na+/K+‐ATPase initiates signal cascades independent of changes in intracellular Na+ and Ca2+ concentrations, J. Biol. Chem., 275, 27838, 10.1074/jbc.M002950200

10.1074/jbc.M107892200

10.1152/ajpheart.2001.281.5.H1899

Golomb E., 1994, Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells, Am. J. Hypertens., 7, 69, 10.1093/ajh/7.1.69

10.1016/S0022-5347(05)66157-5

10.1074/jbc.M106178200

10.1073/pnas.221315298

10.1074/jbc.272.38.23905

10.1006/taap.1998.8471

Contreras R.G., 1999, Relationship between Na+/K+‐ATPase and cell attachment, J. Cell Sci., 112, 4223, 10.1242/jcs.112.23.4223

10.1046/j.1432-1033.2002.02911.x

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FEBS Journal

Tập 269 Số 10

2434-2439

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