© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Signalling via stress-activated mitogen-activated protein kinases in the cardiovascular system
Department of Biochemistry, University of Western Australia, Nedlands 6907, Australia
* Tel.: +61-8-9380-1348; fax: +61-8-9380-1148 marieb{at}cyllene.uwa.edu.au
A number of physiological, pharmacological and pathological stimuli initiate cardiac hypertrophy. The intracellular signalling events activated by these stimuli are equally complex. Our ability to treat the hypertrophic and failing myocardium effectively will require clarification of which signalling events regulate growth, remodelling and failure. Much recent attention has focused on the regulation of the mitogen-activated protein kinase cascades (MAPKs), with the importance of these cascades in the development of cardiovascular diseases being extensively explored. These signalling pathways may provide one link from the diverse stress and pharmacological extracellular stimuli to the regulation of gene expression, contractile protein regulation and protein function. This review focuses on the recent progress made in the understanding of the regulation and function of MAPKs in the cardiovascular system, with particular emphasis being placed on the events in the cardiac ventricular myocyte.
KEYWORDS ANF, Atrial Natriuretic Factor; BMK, Big Mitogen-activated protein Kinase (=ERK5); CSBP, Cytokine Suppressive Anti-Inflammatory Drug; Binding Protein (=p38 MAPK); CT, Cardiotrophin; ERK, Extracellular signal Regulated protein Kinase; FAK, Focal Adhesion Kinase; G-protein, GTP-binding-protein; GDS, Guanine nucleotide dissociation stimulator; IL, Interleukin; JNK, c-Jun-N-terminal protein Kinase; LIF, Leukemic Inhibitory Factor; MAPK, Mitogen-Activated Protein Kinase; MAPKAPK, MAPK-Activated Protein Kinase; MEK, Mitogen-activated protein kinase(or ERK) kinase; MEKK, MEK kinase; MKK, Mitogen-activated protein Kinase Kinase; MKP, MAPK phosphatase; Mnk, MAPK interacting kinase; MSK, Mitogen- and Stress-Activated Kinase 1; Mxi2, Max interacting protein2 (=p38 MAPK); p38, protein kinase 38 kDa; p90RSK, 90kDa Ribosomal S6 Kinase; PDGF, Platelet Derived Growth Factor; PI3K, Phosphatidylinositol 3'Kinase; PKC, Protein Kinase C; Ral.GDS, Ral guanine nucleotide dissociation stimulator; RK, Reactivating Kinase (=p38 MAPK); ROS, Reactive Oxygen Species; SAPK, Stress Activated protein Kinase; SRE, Serum Response Element; TNF, Tumour Necrosis Factor
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