Cardiac expression and subcellular localization of the p38 mitogen-activated protein kinase member, stress-activated protein kinase-3 (SAPK3)

被引:49
作者
Court, NW
dos Remedios, CG
Cordell, J
Bogoyevitch, MA
机构
[1] Univ Western Australia, Dept Biochem, Cell Signalling Lab, Crawley, WA 6009, Australia
[2] Univ Sydney, Dept Anat & Histol, Muscle Res Unit, Inst Biomed Res F13, Sydney, NSW 2006, Australia
[3] Inst Canc Res, Chester Beatty Labs, Hybridoma Unit, London SW3 6JB, England
[4] Western Australia Inst Med Res, Perth, WA 6000, Australia
基金
英国医学研究理事会;
关键词
mitogen-activated protein kinases; stress-activated protein kinases; p38 mitogen-activated protein kinases; cultured cardiac myocytes; syntrophin;
D O I
10.1006/jmcc.2001.1523
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
N. W. COURT, C. G. Dos REMEDIOS, J. CORDFILL AND M. A. BOGOYEVITCH. Cardiac Expression and Subcellular Localization of the p38 Mitogen-activated Protein Kinase Member, Stress-activated protein Kinase-3 (SAPK3). journal of Molecular and Cellular Cardiology (2002) 34, 413-426. Despite the interest in the roles that mitogen-activated protein kinases (MAPKs) play in the heart, the role of the different MAPK isoforms has been relatively poorly defined. A third isoform of p38 MAPK, known variously as stress-activated protein kinase-3 (SAPK3), p38-, or ERK6, has been previously shown to differ from p38-alpha/beta both in its molecular weight and its lack of inhibition by the compound SB203580. We have generated monoclonal antibodies with specificity for SAPK3 demonstrated by immunoblot analysis, immunofluorescence studies, and cloning of SAPK3 front a rat heart cDNA expression library. By immunoblotting, we confirmed high expression of SAPK3 in fast, slow and mixed fibre types of murine skeletal muscle and observed significant expression restricted to heart, lung, thymus and testes. In addition to expression in normal heart (human, mouse. rat, dog and pig), we observed constant expression in diseased human heart, as well as control and hypertrophic Cultured neonatal rat cardiac myocytes. Immunolocalization in cultured cardiac myocytes followed by confocal microscopy showed punctate, non-nuclear SAPK3 staining. In contrast, p38-alpha/beta staining was non-punctate and distributed throughout the cytosol and nucleus. Whereas treatment with Leptomycin B to prevent nuclear export processes promoted higher levels of p38-alpha/beta staining in cardiac myocyte nuclei, there was no apparent change in SAPK3 localization under these conditions. These differences between p38-alpha/beta and SAPK3 probably reflect the spccialized functions of SAPK3 and emphasize the need to evaluate SAPK3 upstream activators and downstream targets in the heart. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:413 / 426
页数:14
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