Abstract
We investigated the activation of mitogen-activated protein kinases (MAPKs) pathways by purinergic stimulation in cardiac myocytes from adult rat hearts. ATPγS increased the phosphorylation (activation) of the extracellular signal regulated kinase 1 and 2 (ERK1/2) and p38 MAPK. ERK1/2 and p38 MAPK activation was differential, ERK1/2 being rapid and transient while that of p38 MAPK slow and sustained. Using selective inhibitors, activation of ERK1/2 was shown to involve protein kinase C and MEK1/2 while that of p38 MAPK was regulated by both protein kinase C and protein kinase A. Further more, we show that purinergic stimulation induces the phosphorylation of the MAPK downstream target; mitogen- and stress-activated protein kinase 1 (MSK1), in cardiac myocytes. The time course of MSK1 phosphorylation closely follows that of ERK activation. Inhibitors of the ERK and p38 MAPK pathways were tested on the phosphorylation of MSK1 at two different time points. The results suggest that ERKs initiate the response but both ERKs and p38 MAPK are required for the maintenance of the complete phosphorylation of MSK1. The temporal relationship of MSK1 phosphorylation and cPLA2 translocation induced by purinergic stimulation, taken together with previous findings, is an indication that cPLA2 may be a downstream target of MSK1. (Mol Cell Biochem 242: 163–171, 2003)
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Abbreviations
- ERK:
-
extracellular signal-regulated kinase
- MAPK:
-
mitogen-activated protein kinase
- MSK1:
-
mitogen- and stress-activated protein kinase-1
- PKA:
-
protein kinase A
- PKC:
-
protein kinase C
- PKI:
-
cAMP dependent protein kinase inhibitor
- PLA2 :
-
phospholipase A2
References
Vassort G: Adenosine 5’-triphosphate: A P2-purinergic agonist in the myocardium. Physiol Rev 81: 767–806, 2001
Legssyer A, Poggioli J, Renard D, Vassort G: ATP and the other adenine compounds increase mechanical activity inositol triphosphate production in rat heart. J Physiol 401: 185–199, 1988
Kuzmin AI, Lakomkin VL, Kapenko VI, Vassort G: Interstitial ATP level and degradation in control and postmyocardial infracted rats. Am J Physiol 275, C766 — C771, 1998
Fredholm BB, Abbracchio MP, Bumstock G, Dubyak GR, Harden TK, Jacobson KA, Schwabe U, Williams M: Towards a revised nomenclature for PI and P2 receptors. Trends Pharmacol Sci 18: 79–82, 1997
Ralevic V, Burnstock G: Receptors for purines and pyrimidines. Pharmacol Rev 50: 415–492, 1998
Communi D, Govaerts C, Parmentier M, Boeynaems JM: Cloning of a human purinergic P2Y receptor coupled to phospholipase C and adenyl cyclase. J Biol Chem 272: 31969–31973, 1997
Puceat M, Roche S, Vassort G: Src family tyrosine kinase regulates intracellular pH in cardiomyocytes. J Cell Biol 141: 1637–1646, 1998
Almond F, Fauzier J-M, Bony C, Vassort G: Simultaneous activation of p38 MAPK and p44/42 MAPK by ATP stimulates the K’ current ITREK in cardiomyocytes. J Biol Chem 275: 39110–39116, 2000
Leslie CC: Properties and regulation of cytosolic phospholipase A2. J Biol Chem 272: 16709–16712, 1997
Gijon MA, Leslie CC: Regulation of arachidonic acid release and cytosolic phospholipase A2 activation. J Leukoc Biol
Gijon MA, Spencer DM, Kaiser AL, Leslie CC: Role of phosphorylation sites and the C2 domain in regulation of cytosolic phospholipase Al. J Cell Biol 145: 1219–1232, 1999
Sugden PH, Clerk A: Cellular mechanisms of cardiac hypertrophy. J Mol Med 76: 725–746, 1998
Widmann C, Gibson S, Jarpe MB, Johnson GL: Mitogen-activated protein kinase: Conservation of a three kinase module from yeast to human. Physiol Rev 79: 143–180, 1999
Della Roca GJ, van Viesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz Ri: Ras-dependent initogen-activated protein kinase activation by G protein-coupled receptors. Convergence of Gi-and Gqmediated pathways on calcium/calmodulin, Pyk2 and Src kinase. J Biol Chem 272: 19125–19132, 1997
Lazou A, Fuller JS, Bogoyevitch AM, Orfali AK, Sugden HP: Characterization of stimulation of phosphoinositide hydrolysis by a,-adrenergic agonists in adult rat hearts. Am J Physiol 267: H970 — H978, 1994
Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR: PD098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem 270: 27489–27494, 1995
Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, Feeser WS, Van Dyk DE, Pitts WJ, Earl RA, Hobbs F, Copeland RA, Magolda RL, Scherle PA, Trzaskos JM: Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem 273: 1862318632, 1998
Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E, Loriolle F, Duhamel L, Charon D, Kirilovsky J: The bisindolylmaleimide GF109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem 266: 15771–15781, 1991
Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, Strickler JE, McLaughlin MM, Siemens IR, Fisher SM, Livi GP, White JR, Adams JL, Young PR: A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372: 739–746, 1994
Frantz B, Klatt T, Pang M, Parsons J, Rolando A, Williams H, Tocci MJ, O’Keefe SJ, O’Neill MA: The activation state of p38 mitogenactivated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding. Biochemistry 37: 1384613853, 1998
Yamboliev IA, Hedges JC, Mutnick JL, Adam LP, Gerthoffer WT: Evidence for modulation of smooth muscle force by the p38 MAP kinase/Hsp27 pathway. Am J Physiol 278: H1899 - H1907, 2000
Deak M, Clifton AD, Lucocq JM, Alessi DR: Mitogen-and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38 and may mediate activation of CREB. EMBO J 17: 44264441, 1998
Hefner Y, Borsch-Haubold G, Murakami M, Wilde JI, Pasquet S, Schieltz, Ghomashchi F, Yates JR III, Armstrong CG, Paterson A, Cohen P, Fukunaga R, Hunter T, Kudi I, Watson SP, Gelb MH: Serine 7272 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. J Biol Chem 275: 37542–37551, 2000
Antonysamy MA, Moticka EJ, Ramkurar V: Adenosine acts as an endogenous modulator of IL-2 dependent proliferation of cytotoxic T lymphocytes. J Immunol 15: 2813–2831, 1995
Abbracchio MP, Burnstock G: Purinergic signaling: Pathophysiological roles. Jpn J Pharmacol 78: 113–145, 1998
Zheng JS, Boluyt MO, O’Neil L, Crow MT, Lakatta EG: Extracellular ATP induces immediate-early gene expression but not cellular hypertrophy in neonatal cardiac myocytes. Cire Res 74: 1034–1041, 1994
Zheng JS, Boluyt MO, Long X, O’Neil L, Lakatta EG, Crow MT: Extracellular ATP inhibits adrenergic agonist-induced hypertrophy of neonatal cardiac myocytes. Circ Res 78: 525–535, 1996
Post GR, Goldstein D, Thuerauf DJ, Glembotski CC, Brown JH: Dissociation of p44 and p42 mitogen activated protein kinase activation from receptor-induced hypertrophy in neonatal rat ventricular myocytes. J Biol Chem 271: 8452–8457, 1996
Bogoyevitch MA, Glennon PE, Andersson MB, Clerk A, Lazou A, Marshall JC, Parker PJ, Sugden PH: Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy. J Biol Chem 269: 1110–1119, 1994
Clerk A, Michael A, Sugden PH: Stimulation of the p38 mitogen-activated protein kinase pathway in neonatal rat ventricular myocytes by the G protein-coupled receptor agonists, endothelin-1 and phenylephrine: A role in cardiac myocyte hypertrophy? J Cell Biol 142: 523535, 1998
Puceat M, Bony C, Jaconi M, Vassort G: Specific activation of adenyl cyclase V by purinergic agonists. FEBS Lett 431: 189–194, 1998
Gao Z, Chen T, Weber MJ, Linden J: A2B adenosine and P2YZ receptors stimulate mitogen-activated protein kinase in human embryonic kidney-293 cells. Cross-talk between camp and protein kinase C pathways. J Biol Chem 274: 5972–5980, 1999
Bogoyevitch MA, Marshall CJ, Sugden PH: Hypertrophie agonists stimulate the activities of the protein kinases c-Raf and A-Raf in cultured ventricular myocytes. J Biol Chem 270: 26303–26310, 1995
Thomson S, Clayton AL, Hazzalin CA, Rose S, Barrat MJ, Mahadevan LC: The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. EMBO J 18: 4779–4793, 1999
Arthur JSC, Cohen P: MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells. FEBS Left 482: 44–48, 2000
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Markou, T., Vassort, G., Lazou, A. (2003). Regulation of MAPK pathways in response to purinergic stimulation of adult rat cardiac myocytes. In: Kardami, E., Hryshko, L., Mesaeli, N. (eds) Cardiac Cell Biology. Developments in Molecular and Cellular Biochemistry, vol 39. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4712-6_21
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DOI: https://doi.org/10.1007/978-1-4757-4712-6_21
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