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肖瑞平——北京大学——心血管信号转导、心血管药理学与生物学

  1. 肖瑞平,北京大学

来源:生物谷 2016-07-26 17:35

心血管信号转导、心血管药理学与生物学

导师姓名:肖瑞平         导师类别:博士生导师  

  • 姓名: 肖瑞平       性别: 女       出生年月:
  • 所在院校: 北京大学       所在院系: 生命科学学院
  • 职称: 教授       招生专业: 细胞生物学
  • 研究领域: 心血管信号转导、心血管药理学与生物学
  • 联系方式

  • E-Mail: imm@pku.edu.cn       电话:       邮编: 100871
  • 地址: 北京市海淀区颐和园路5号北京大学英杰交流中心322室
  • 个人简介

      肖瑞平,女,1962年11月生于湖北大冶,现任北京大学心血管研究所所长、教育部分子心血管学重点实验室学术委员会主任、国家“长江计划”特聘教授,国家杰出青年科学基金获得者。
      肖瑞平教授自80年代末开始研究心脏β肾上腺素受体亚型(β-AR)信号传导,20年科研求索之旅中,系统地研究了心肌细胞β-AR的信号转导机制及其生理学、病理学意义,取得了一系列重要成果。于90年代初首先发现β2-AR可同时与功能相反的Gs和Gi蛋白耦联,从而对受体仅与单一G蛋白耦联的传统理论提出挑战,获国际心脏学会理查德·冰奖(决赛奖)。在随后的进一步研究中,她发现β2-AR与Gi的耦联不仅对Gs介导的cAMP信号起屏障作用,选择性地激活靶蛋白,更重要的是产生Gs-cAMP非依赖性的信号传导。率先阐明了β1-AR和β2-AR具有相反的功能 。进一步,她们又独树一帜,提出β1-AR细胞凋亡信号由钙信号和钙依赖性蛋白激酶II,而非经典的cAMP和蛋白激酶A所介导。她的上述发现与突破向传统观念提出了挑战,为受体G蛋白信号转导的研究开辟了新领域;为心衰的病理生理及临床治疗开启了新的思路;同时也为构筑受体亚型多样性与共存性的理论基础奠定了一块基石。她的这些研究工作得到了国际心血管研究及受体信号转导领域同行的广泛认同。迄今已在国际一流学术刊物上发表论文100余篇,引用4500次以上。
      2000-2010年任心血管领域最高杂志《Circulation Research》两届编委,1999年至今任《Journal of Molecular and Cellular Cardiology》编委,同时还担任新创刊的 《Disease Models and Mechanisms》的首任编委(http://dmm.biologists.org/site/misc /edboard.xhtml)。为《Science STK》、《Circulation》、《Circulation Research》、《Trends in Pharmacological Sciences》、《Trends in Cardiovascular Medicine》、《Cardiovascular Research》、和《Journal of Molecular and Cellular Cardiology》等撰写特邀综述(Invited Reviews)或编辑评论(Editorial)。   作为转化医学的先行者之一,肖瑞平教授在将转化医学的概念引入中国的同时也在身体力行地进行推广,她认为中国在这一新领域能够有所作为(Nature 2004, 432:A44-47)。自2003年起筹建北京大学分子医学研究所(IMM),2005年1月北京大学分子医学研究所正式成立,肖瑞平教授担任所长。至今,北京大学分子医学研究所以独特的机制运行并已获高水平研究成果,已成为我国心血管科学研究领域与国际接轨的桥梁。

    著作及论文

    Zheng, M., Xiao, R.P.: Role of Mitofusin-2 in Cardiovascular Oxidative Stress. J. Mol. Med. 2010, 88:987-991. Talan, M.I.,Ahmet, I., Xiao, R.P., Lakatta, E.G.:beta2-AR Agonists in Treatment of Chronic Heart Failure: Long Path to Translation. J Mol. Cell. 2010 Oct1. [Epub ahead of print]. Zhang, Y., Cao, C.M., Xiao, R.P.: Kinase Activity-Independent Anchoring Function of Protein Kinase Cd. Am J Physiol Cell Physiol.2010, in press. Wang, X., Xie, W., Zhang, Y., Lin, P., Han, L., Han, P., Wang, Y., Chen, Z., Ji, G., Zheng, M., Weisleder, N., Xiao, R.P., Takeshima, H., Ma. J, Cheng, H.: Cardioprotection of ischemia/reperfusion injury by cholesterol-dependent MG53-mediated membrane repair. Circ Res. 107:76-83, 2010. Cao, C.M., Zhang, Y., Weislede, N., Ferrante, C., Wang, X.H., Lv, F., Zhang, Y., Song, R.S., Hwang, M., Jin, L., Guo, J., Peng, W., Li, G., Nishi, M., Takeshima, H., Ma, J., Xiao, R.P.: MG53 constitutes a primary determinant of cardiac ischemic preconditioning. Circulation. 121: 2565-74, 2010. Jozwiak, K., Toll, L., Jimenez, L., Woo, A.Y., Xiao, R.P., Wainer, I.W.: The effect of stereochemistry on the thermodynamic characteristics of the binding of fenoterol stereoisomers to the beta(2)-adrenoceptor. Biochem Pharmacol. 79:1610-5, 2010. Jozwiak, K., Woo, A.Y.H., Tanga, M.J., Toll, L., Jimenez, L., Kozocas, J.A., Plazinska, A., Xiao, R.P., Wainer, I.W.: Comparative Molecular FieldAnalysis of Fenoterol Derivatives: A Platform Towards Highly Selective and Effective beta2-Adrenergic Receptor Agonists. Bioorganic & Medicinal Chemistry. 18:728-36, 2010. Li, Q., Li, G., Lan, X., Zheng, M., Chen, K.H., Cao, C., Xiao, R.P.: Receptor Interacting Protein 3 Suppresses Vascular Smooth Muscle Cell Growth by Inhibition of PI3K-Akt Axis. J. Biol. Chem. 285:9535-44, 2010. Tsang, S., Woo, A.Y.H., Zhu, W., Xiao, R.P.: Deregulation of RGS2 in Cardiovascular Diseases. Frontiers in Bioscience. 2:547-57, 2010. Ekhterae, D., Hinmon, R., Zeeshan, A., Parish, L., Zhu W., Xiao, R.-P., Gorman, R.C., Gorman, J.H.: Infarction Induced Myocardial Apoptosis and ARC Activation. J Surg Res.. 2010, Jun 6. [Epub ahead of print] Peng, W., Zhang, Y., Zheng, M., Cheng, H., Zhu, W., Cao, C.M.*, Xiao, R.P.*: Cardioprotection by CaMKII-δB is mediated by phosphorylation of HSF1 and subsequent expression of inducible HSP70. Circulation Research, 2009 Nov 12. [Epub ahead of print]. Ekhterae, D., Hinmon, R., Zeeshan, A., Parish, L., Zhu W., Xiao, R.-P., Gorman, R.C., Gorman, J.H.: Infarction Induced Myocardial Apoptosis and ARC Activation.Journal of Thoracic and Cardiovascular Surgery. 2009, Jun 6. [Epub ahead of print]. Peng, W., Zhang, Y., Zhu, W., Cao, C.M., Xiao, R.P.: AMPK and TNF-a at the Crossroad of Cell Survival and Death in Ischemic Heart. Cardiovasc Res. 2009, 84(1):1-3. Chakir, K., Daya, S., Tunin, R.S., Liang, H.Y., Abraham, T., Lai, E. W., Pacak, K., Xiao, R.P., Tomaselli, G. F., Kass, D. A.: Mechanisms of Enhanced Beta-adrenergic Reserve From Cardiac Resynchronization Therapy. Circulation. 2009, 119:1231-40. Pang, J., Zeng, X., Xiao, R.P., Lakatta, E.G., Lin, L.: Design, generation, and testing of mammalian expression modules that tag membrane proteins. Protein Sci. 2009; 18:1261-71 Lee, D.I., Klein, M.G., Zhu, W., Xiao, R.P., Gerzanich, V., Xu, K.Y.: Activation of (Na++K+)-ATPase Modulates Cardiac L-Type Ca2+ Channel Function. Mol Pharmacol. 2009, 75:774-81. Woo, A.Y.H., Wang, T.B., Zhu, W., Abernethy, D., Wainer, I., Xiao, R.P.: Stereochemistry of an agonist determines coupling preference of beta2-adrenoceptor to different G proteins in cardiomyocytes. Mol. Pharmacol. 2009;75:158-65. Ahmet, I., Krawczyk, M., Zhu, W., Woo, A., Morrell, C., Poosala, S., Xiao, R.P., Lakatta, E.G., Talan, M.: Cardioprotective and survival benefits of long-term combined therapy with β2AR Agonist and β1AR Blocker in dilated cardiomyopathy post-myocardial infarction. JPET. 325:491-9, 2008. Luo, D., Yang, D., Lan, X., Li, K., Li, K., Chen, J., Zhang, Y., Xiao, R.P., Han, Q., and Cheng, H.: Perinuclear Ca2+ Waves in developing cardiac myocytes:Inositol 1,4,5-trisphosphate receptor regulation of nuclear Ca2+ signaling Cell. Calcium. 43:165-74, 2008. Guo, X., Chen K.H., Li, Q., Liao, H., Zhang, J., Tang, J., and Xiao, R.P. Mitofusin-2 induces vascular smooth muscle apoptosis via mitochondrial death pathway. Circ. Res. 101:1113-22, 2007. Shen, T, Zheng, M., Cao, C., Chen, L., Zhang, W., Cheng, H., Tong, J., Chen, K.H., and Xiao, R.P.: Mitofusin-2 is a major determinant of oxidative stress-mediated heart muscle cell apoptosis. J. Biol. Chem. 282:23354-23361,2007. Jozwiak K., Khalid C., Tanga M.J., Berzetei-Gurske I., Jimenez L., Kozocas J.A., Woo A., Zhu W., Xiao, R.P., Abernethy D.R., Wainer I.W. Comparative Molecular Field Analysis (CoMFA) of the Binding of the Stereoisomers of Fenoterol and Fenoterol Derivatives to the beta2 Adrenergic Receptor. J. Med. Chem. 2007, 50:2903-2915, 2007. Zhu, W.Z., Woo, A. Y.-H., Yang, D., Cheng, H., Crow, M.T., Xiao, R.P. Activation of CaMKIIdc is a common intermediate of diverse death stimuli-induced heart muscle cell apoptosis. J Biol Chem, 282:10833-10839, 2007. Yang, D., Zhu, W.Z., Xiao, B., Brochet, D., Chen, W., Lakatta, E.G.,, Xiao, R.P., Cheng, H. Ca2+/Calmodulin kinase II -dependent phosphorylation of ryanodine receptors suppresses spontaneous Ca2+ release in cardiac myocytes, Circ Res. 2007, 100:399-40. Vinogradova, T.M., Lyashkov, A.E., Zhu, W., Ruknudin, A.M., Sirenko, S., Yang, D., Deo, S., Barlow, M., Johnson, S., Caffrey, J.L., Zhou, Y.Y., Xiao, R.P., Cheng, H., Stern, M.D., Maltsev, V.A. and Lakatta, E.G..: High basal protein kinase A-dependent phosphorylation drives rhythmic internal Ca2+ store oscillations and spontaneous beating of cardiac pacemaker cells. Circ. Res. 98:505-514, 2006. Yang, Y., Zhu, W.Z., Joiner, M.L., Zhang, R., Oddis, C.V., Hou, Y., Yang, J., Price, E.E., Gleaves, L., Eren, M., Ni, G., Vaughan, D.E., Xiao, R.P., Anderson, M.E. Calmodulin Kinase II inhibition protects against myocardial apoptosis in vivo by phospholamban-dependent and –independent mechanisms. Am J Physiol Heart Circ Physiol. 2006,291:H3065-75. Beigi, F., Bertucci, C., Zhu, W., Chakir, K., Wainer, I.W., Xiao, R.P., Abernethy, D.R. Enantioselective separation and online affinity chromatographic characterization of R,R- and S,S-fenoterol. Chirality. 2006, 18:822-7. Xiao, R.P., Zhu, W.Z., Zheng, M., Cao, C.M., Zhang, Y.Y., Lakatta, E.G., Han ,Q,D.: Subtype-specific alpha1- and beta-adrenoceptor signaling in the heart. Trends Pharmacol Sci. 27: 330-337, 2006 (Invited review). Zhu, W., Zeng, X., Zheng M, Xiao, R.P.: The enigma of cardiac beta2-adrenergic Gi signaling in the heart: the good, the bad, and the ugly. Circ. Res. 97: 507-509, 2005 (Commentary). Zheng, M., Zhu, W., Han, Q., Xiao, R.P.: Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling. Pharmacol. Ther. 108: 257-68, 2005 (Invited Review). Zhu, W.Z., Yang, D., Zhang, S.J., Chakir, K., Cheng, H., Lavoie, C., Mercier, J.F., Bouvier, M., Hébert, T.E., Lakatta, E.G., Xiao, R.P.: Dimerization of beta1- and beta2-adrenergic receptor subtypes optimizes beta-adrenergic modulation of cardiac contractility. Circ. Res. 97: 244-251, 2005. Luo, D., Sun, H., Xiao, R.P., & Han, Q. Caffeine induced Ca2+ release and capacitative Ca2+ entry in human embryonic kidney (HEK293) cells. Eur. J. Pharmacol., 509: 109-115, 2005. Xu, X., Yang, D., Ding, J., Wang, W., Chu, P.H., Dalton, N.D., Wang, H.Y., Bermingham, J.R. Jr., Ye, Z., Liu, F., Rosenfeld, F.G., Manley, J.L., Ross, J. Jr., Chen, J., Xiao, R.P., Cheng H., and Fu, X.D. ASF/SF2-regulated postnatal reprogramming of CaMKIId alternative splicing modulates excitation-contraction coupling in cardiac muscle. Cell. 120: 59-72, 2005. Zheng, M., Jo, S.H., Wersto, R., Han, Q., and Xiao, R.P.: Intracellular acidosis-induced p38 MAPK activation and its pathophysiological relevance in cardiomyocyte ischemia. FASEB J. 19: 109-111, 2005. Wang, W., Zhu, W., Wang, S., Yang, D., Crow, M.T., Xiao, R.P., Cheng, H.: Sustained b1-adrenergic stimulation modulates cardiac contractility by Ca2+/calmodulin kinase signaling pathway. Circ. Res. 95: 798-806, 2004. Leblais, V., Jo, S.H., Chakir, K., Maltsev, V., Zheng, M., Crow, M.T., Wang, W., Lakatta, E.G., and Xiao, R.P.: Phosphatidylinositol 3-kinase offsets camp-mediated positive inotropic effect via inhibiting Ca2+ influx in cardiomyocytes. Circ. Res. 95: 1183-1190, 2004. Beigi, F., Chakir, K., Xiao, R.P., and Wainer, I.W.: G-protein-coupled receptor chromatographic stationary phases ii: ligand-induced conformational mobility on an immobilized beta2-adrenergic receptor. Anal. Chem. 76: 7187-7193, 2004. Zheng, M., Hou, R., Han, Q., and Xiao, R.P.: Different regulation of erk1/2 activation by beta-adrenergic receptor subtypes in adult mouse cardiomyocytes. Heart, Lung & Circulation. 13: 179-184, 2004. Zheng, M., Hou, R., and Xiao, R.P.: Acidosis-induced p38 MAPK activation and its implication in regulation of cardiac contractility. Acta Pharmacol Sin. 25: 1299-1305, 2004. Chen, K.H., Guo, X.M., Ma, D.L., Guo, Y.H., Li, Q., Li, P., Qiu, X., Xiao*, R.P., and Tang, J.: Dysregulation of a novel hyperplasia suppressor gene triggers vascular proliferative disorders. Nature Cell Biology, 6: 872-883, 2004 (* The corresponding author). Pepe, S., van den Brink, O.W.V., Lakatta, E.G., and Xiao, R.P.: beta-adrenergic receptor-opioid peptide receptor cross-talk: cardiovascular regulation and adaptation in health and disease. Cardiovascular Research. 15;63:414-22, 2004 (Invited review). Xiao, R.P., Zhu, W., Zheng, M., Bond, R., Lakatta, E.G., and Cheng, H.: Subtype-specific beta-adrenergic signaling pathways and their clinical implications. Trends Pharmacol Sci. 25: 358-365, 2004 (Invited review) Patterson, A.J., Zhu, W., Chow, A., Kosek, J., Xiao, R.P., and Kobilka, B.K.: Protecting the myocardium: A role for the beta2-Adrenergic receptor in the heart. Critical Care Medicine. 32: 1041-1048, 2004. Ding, J.H., Xu, X., Yang, D., Chu, P.H., Dalton, N.D., Ye, Z., Yeakley, J.M., Cheng, H., Xiao, R.P., Ross, J., Chen, J., and Fu, X.D.: Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart. EMBO J. 23: 885-896, 2004. Xiao, R.P., and Balke, C,W,: Na+/Ca2+ Exchange Linking beta2-Adrenergic Gi Signaling to Heart Failure: Associated Defect of Adrenergic Contractile Support. J Mol. Cell. Cardiol. 36: 7-11, 2004 (Editorial). Chu, G., Egnaczyk, G.F., Zhao, W., Jo, S.H., Fan, G.C., Maggio, J.E., Xiao, R.P., and Kranias, E.G.: Phosphoproteome Analysis of Cardiomyocytes Subjected to beta-Adrenergic Stimulation: Identification and Characterization of a Novel Heat Shock Protein. Circ. Res. 94: 184-193, 2004. Xiao, R.P., Cheng, H., Zhoum Z., Chenm Y., Wum C. and Gum X.C.: Is china ready to go mainstream in molecular medicine China Voices II (Supplement to nature). 432: A42-A45, 2004. Cheng, A., Wang, S., Yang, D., Xiao, R.P., and Mattson, M.: Calmodulin mediates BDNF cell survival signaling upstream of Akt kinase in embryonic neocortical neurons. J. Biol. Chem. 278: 7591-7599, 2003. Zhu, W.Z., Wang, S.Q., Chakir, K., Kolbilka, B.K., Cheng, H., and Xiao, R.P.: Linkage of beta1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/Calmodulin Kinase II. J. Clin. Invest. 111: 617-625, 2003. Sasaki, N., Murata, M., Guo, Y., Jo, S.H., Ohler, A., Akao, M., O’Rourke, B., Xiao, R.P., Bolli, R., and Marban, E.: MCC-134, a single pharmacolphore, opens surface adenosine triphosphate-sensitive potassium channels, blocks mitochondrial adenosine triphosphate-sensitive potassium channels, and suppresses preconditioning. Circulation. 107: 1183-1188, 2003. Yang, D., Zhu, W.Z., Chakir, K., Wang, W., Wu, C., Wang, Y., Xiao, R.P., Chen, W.S., and Cheng, H.: calmodulin regulation of excitation-contraction coupling in cardiac myocytes. Circ. Res. 92: 659-667, 2003. Chakir, K., Xiang, Y., Zhang, S.J., Yang, D., Cheng, H., Kobilka, B.K., and Xiao, R.P.: The third intracellular loop and the carboxyl terminus of beta2-adrenergic receptor confer the receptor spontaneous activity. Mol. Pharmacol. 64: 1048-1058, 2003. Xiao, R.P., Zhang, S.J. Kuschel, M., Zhou, Y.Y., Bond, R.A., Balke, C.W., Lakatta, E.G., and Cheng, H.: Enhanced Gi signaling mediates the diminution of beta2-adrenergic contractile response in failing spontaneous hypertensive rat heart. Circulation. 108:1633-1639, 2003. Song, L.S., Guia, A., Muth, J.N., Wang, S.Q., Xiao, R.P., Josephson, I.R., Schwartz, A., Lakatta, E.G., and Cheng, H.: Ca2+ signaling in hypertrophic transgenic cardiac myocytes overexpressing the α1 subunit of L-type Ca2+ channel. Circ. Res. 90: 174-181, 2002. Liao, P., Wang, S.Q., Zheng, M., Zheng, M.Z., Cheng, H., Wang, Y., and Xiao, R.P.: p38 mitogen activated protein kinase mediates negative inotropic effect in cardiac myocytes. Circ. Res. 90: 190-196, 2002. Hagemann, D., and Xiao, R.P.: Dual site phospholamban phosphorylation and its physiological relevance in the heart. Trends Cardiovasc Med. 12: 51-56, 2002 (Invited review). Jo, S.H., Leblais, V., Crow, M.T., and Xiao, R.P.: Phosphatidylinositol 3-kinase functionally compartmentalizes the concurrent Gs signaling during beta2-adrenergic stimulation. Circ. Res. 91: 46-53, 2002. Lavoie, C., Mercier, J.F., Salahpour, A., Umapathy, D., Breit, A., Villeneuve, L.R., Zhu, W.Z., Xiao, R.P., Lakatta, E.G., Bouvier, M., and Hébert, T.E.: beta1/beta2-adrenergic receptor heterodimerization regulates beta2-adrenergic receptor internalization and ERK signaling efficacy. J. Biol. Chem. 277: 35402-35410, 2002. Zhu, W.Z., Zheng, M., Lefkowitz, R.J., Koch, W.J., Kobilka, B., and Xiao, R.P.: Dual modulation of cardiac cell survival and cell death by beta2-adrenergic signaling in adult mouse heart cells. Proc. Nat. Acad., Sci. USA 98: 1607-1612, 2001. Song, L.S., Wang, S.Q., Xiao, R.P., Spurgeon, H., Lakatta, E.G., and Cheng, H.: beta-adrenergic stimulation synchronizes intracellular Ca2+ release during excitation-contraction coupling in cardiac myocytes. Circ. Res. 88: 794-801, 2001. Liao, P., Georgakopoulos, D., Kovacs, A., Zheng, M., Lerner, D., Pu, H., Saffitz, J., Chien, K., Xiao, R.P., Kass, D.A. and Wang, Y.: The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy. Proc. Nat. Acad., Sci. USA 98: 12283-12288, 2001. Xiao, R.P.: β-adrenergic signaling in the heart: Dual coupling of the β2-adrenergic receptor to Gs and Gi proteins. Science’s STKE. 16: RE15, 2001 (Invited review). Zhang, S.J., Cheng, H., Zhou Y.Y., Wang, D.J., Zhu, W., Ziman, B., Spurgeon, H., Lefkowitz, R.J., Lakatta, E.G., Koch, W.J., and Xiao, R.P.: Inhibition of spontaneous beta2-adrenergic activation rescues beta1-adrenergic contractile response in cardiomyocytes overexpressing beta2-adrenoceptor. J. Biol. Chem. 275: 21773-21779, 2000. Hagemann, D., Kuschel, M., Kuromochi, T., Zhu, W., Cheng, H., and Xiao, R.P.: Frequency-encoding Thr17 phospholamban phosphorylation is independent of Ser16 phosphorylation in cardiac myocytes. J. Biol. Chem. 275: 22532-22536, 2000. Zhou, Y.Y., Wang, S.Q., Zhu, W., Chruscinski, A., Kobilka, B., Ziman, B., Wang, S., Lakatta, E.G., Cheng, H., and Xiao, R.P.: High efficient adenovirus-directed gene transfer in cultured adult mouse ventricular myocytes. Am. J. Physiol. 279: H429-H436, 2000. Vinogradova, T.M., Zhou, Y.Y., Bogdanov, K.Y., Kuschel, M., Cheng, H., and Xiao, R.P.: Sinoatrial node pacemaker activity requires Ca2+/calmodulin-dependent protein kinase II activation. Circ. Res. 87: 760-767, 2000. Xiao, R.P.: Cell logic for dual coupling of a single class of receptors to Gs and Gi proteins. Cric. Res. 87: 635-637, 2000 (Editorial). Zhou, Y.Y., Zhu, W., Zhang, S..J., Wang, D.J., Kobilka, B., Lakatta, E.G., Cheng, H., and Xiao, R.P.: Ligand-independent activation of beta2- but not b1-adrenoceptor overexpressed in beta1/beta2-adrenoceptor double knockout mouse cardiomyocytes. Mol. Pharmacol. 58: 887-894, 2000. Chen, Y., Xiao*, R.P. Izu, L.T., Cheng, H., Kuschel, M., Spurgeon, H., and Lakatta, E.G.: Gi-dependent localization of beta2-adrenergic receptro signaling to L-type Ca2+ channels. Biophys. J. 79: 2547-2556, 2000 (* The corresponding author). Chesley, A., Ohtani, S., Asai, T., Xiao, R.P., Lunberg, M.S., Lakatta, E.G., and Crow M.T.: beta2-adrenergic receptor delivers an anti-apoptotic signal to cardiac myocytes through Gi-dependent signaling pathways. Circ. Res. 87: 1172-1179, 2000. Zheng, M., Zhang, S.J., Zhu, W., Ziman, B., Kobilka, B.K., and Xiao, R.P.: beta2-adrenergic receptor-induced p38 MAPK activation is mediated by PKA rather than by Gi or Gb in adult mouse cardiomyocytes. J. Biol. Chem. 275: 40635-40640, 2000.

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