Review Signalling via stress-activated mitogen-activated ......Abbreviations: ANF, Atrial...
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Cardiovascular Research 45 (2000) 826–842 www.elsevier.com / locate / cardiores www.elsevier.nl / locate / cardiores Review Signalling via stress-activated mitogen-activated protein kinases in the cardiovascular system * Marie A. Bogoyevitch Department of Biochemistry, University of Western Australia, Nedlands 6907, Australia Received 23 July 1999; accepted 22 October 1999 Abstract 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. 2000 Elsevier Science B.V. All rights reserved. Keywords: Cytokines; Gene expression; Growth factors; Protein kinases; Signal transduction 1. Historical perspective and introduction to the and their close similarity to protein kinases involved in the MAPKs yeast pheromone response recognised [1]. In the following years, the combined experimental results from mammalian In 1988 a protein kinase activated in 3T3-L1 cells in cell biology, biochemistry, and genetic studies in yeast, response to insulin was described. By 1991, two members nematodes and fruit flies allowed the identification of a of this family of protein kinases had been purified, cloned superfamily of related Ser / Thr protein kinases now known as the mitogen-activated protein kinases or MAPKs. Their signature motif is a conserved amino acid sequence Thr– Abbreviations: ANF, Atrial Natriuretic Factor; BMK, Big Mitogen- activated protein Kinase (5ERK5); CSBP, Cytokine Suppressive Anti- X–Tyr (T–X–Y) within their activation loop and phos- Inflammatory Drug; Binding Protein (5p38 MAPK); CT, Cardiotrophin; phorylation of both Thr and Tyr results in their activation ERK, Extracellular signal Regulated protein Kinase; FAK, Focal Adhe- [2]. sion Kinase; G-protein, GTP-binding-protein; GDS, Guanine nucleotide Throughout this review, the MAPKs first recognised to dissociation stimulator; IL, Interleukin; JNK, c-Jun-N-terminal protein respond to growth factor stimulation are referred to as Kinase; LIF, Leukemic Inhibitory Factor; MAPK, Mitogen-Activated Protein Kinase; MAPKAPK, MAPK-Activated Protein Kinase; MEK, Extracellular Signal Regulated Kinases, or ERK MAPKs. Mitogen-activated protein kinase(or ERK) kinase; MEKK, MEK kinase; Principles of the regulation of the ERK MAPKs including MKK, Mitogen-activated protein Kinase Kinase; MKP, MAPK phospha- the regulation by phosphorylation within the T–X–Y motif tase; Mnk, MAPK interacting kinase; MSK, Mitogen- and Stress-Acti- and position within the signal transduction cascades, can vated Kinase 1; Mxi2, Max interacting protein2 (5p38 MAPK); p38, RSK be readily applied to the regulation of the other MAPKs protein kinase 38 kDa; p90 , 90kDa Ribosomal S6 Kinase; PDGF, Platelet Derived Growth Factor; PI3K, Phosphatidylinositol 39Kinase; (Fig. 1). If we first focus on the ERK MAPKs, it is PKC, Protein Kinase C; Ral.GDS, Ral guanine nucleotide dissociation apparent that the two isoforms, ERK1 and ERK2, are stimulator; RK, Reactivating Kinase (5p38 MAPK); ROS, Reactive widely-expressed [1]. In cardiac myocytes, hypertrophic Oxygen Species; SAPK, Stress Activated protein Kinase; SRE, Serum agents activate both isoforms [3]. In vascular smooth Response Element; TNF, Tumour Necrosis Factor *Tel.: 161-8-9380-1348; fax: 161-8-9380-1148. E-mail address: [email protected] (M.A. Bogoyevitch) Time for primary review 35 days. 0008-6363 / 00 / $ – see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S0008-6363(99)00386-7
Review Signalling via stress-activated mitogen-activated ......Abbreviations: ANF, Atrial Natriuretic Factor; BMK, Big Mitogen-signature motif is a conserved amino acid sequence Thr
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