TAILIEUCHUNG - Báo cáo khoa học: 14-3-3 Proteins regulate glycogen synthase 3b phosphorylation and inhibit cardiomyocyte hypertrophy

14-3-3 Proteins are dimeric phophoserine-binding molecules that participate in important cellular processes such as cell proliferation, cell-cycle control and the stress response. In this work, we report that several isoforms of 14-3-3s are expressed in neonatal rat cardiomyocytes. To understand their function, we utilized a general 14-3-3 peptide inhibitor, R18, to disrupt 14-3-3 functions in cardiomyocytes. | ềFEBS Journal 14-3-3 Proteins regulate glycogen synthase 3b phosphorylation and inhibit cardiomyocyte hypertrophy Wenqiang Liao Shuyi Wang Chide Han and Youyi Zhang Institute of Vascular Medicine Peking University Third Hospitaland Key Laboratory of Molecular Cardiovascular Science Ministry of Education Beijing PR China Keywords 14-3-3 proteins cardiomyocyte hypertrophy NFAT PKB GSK3p Correspondence Y. Zhang Institute of Vascular Medicine Peking University Third Hospitaland Key Laboratory of Molecular Cardiovascular Science Ministry of Education Beijing 100083 PR China Fax 86 10 82802306 E-mail zhangyy@ Received 28 September 2004 revised 28 January 2005 accepted 14 February 2005 doi 14-3-3 Proteins are dimeric phophoserine-binding molecules that participate in important cellular processes such as cell proliferation cell-cycle control and the stress response. In this work we report that several isoforms of 14-3-3s are expressed in neonatal rat cardiomyocytes. To understand their function we utilized a general 14-3-3 peptide inhibitor R18 to disrupt 14-3-3 functions in cardiomyocytes. Cardiomyocytes infected with adenovirus-expressing YFP-R18 AdR18 exhibited markedly increased protein synthesis and atrial natriuretic peptide production and potentiated the responses to norepinephrine stimulation. This response was blocked by the pretreatment with LY294002 a phosphoinositide 3-kinase PI3K inhibitor. Consistent with a role of PI3K in the R18 effect R18 induced phosphorylation of a protein cloned from the vakt oncogene of retrovirus AKT8 Akt - also called protein kinase B PKB at Ser473 and glycogen synthase 3 b GSK3b at Ser9 but not extracellular signal-regulated kinase 1 2 ERK1 2 . AdR18-induced PKB and GSK3b phosphorylation was completely blocked by LY294002. In addition a member of the nuclear factor of activated T cells NFAT family NFAT3 was converted into faster mobility forms and translocated into the nucleus upon the .

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